Clonidine in Paediatric Anaesthesia

1
Clonidine in Paediatric Anaesthesia

• MD PhD Henrik Bergendahl
• Smärtavdelningen, Anestesikliniken, Karolinska
  Universitetssjukhuset

2
(No Transcript)
3
Inhibitory and excitatory adrenergic neurones.
McCaughey W, Anaeshetic Physiology and
Pharmacology, Churchill Livingstone, modified
with permission.
4
Sites of heamodynamic action of alpha-2
adrenoceptor agonists. (Eisenach 1996 with
permission.)
5
Sensory cortex, thalamus
Limbic system
Relay regions
NTS
Hypothalamus
RVLM
IML column
Symathetic nerve terminals
Adrenal medulla
Mode of action of antihypertensives. (Prichard
2000 with permission).
6
Non-selective alpha-2 adrenoceptor
agonists Noradrenaline Adrenaline
Selective alpha-2 adrenoceptor agonists Dexmedeto
midine Mivazerol Clonidine Alfa-Methyldopa
Selective and nonselective alpha-2
adrenoceptoragonists. (Khan 1999 with
permission).
7
(No Transcript)
8
A comparison of commonly used preanaesthetics and
clonidine. (Halldin-Lindahl, Anestesi, Liber AB,
modified with permission.)
9

• CLONIDINE IN ADULT ANAESTHESIA
• Better perioperative haemodynamic
  stability Flacke-87, Ghignone 86
• - Reduced stress response after
  intubation Flacke 87
• - Reduced narcotic requirements by 40 Bloor
  82, Flacke -87
• - Net reduction in myocardial oxygen
  consumption Zochowski 84.
• - Little or no effect on respiration in normal
  doses Ooi 91

10

• CLONIDINE IN ADULT ANAESTHESIA
• No interaction with opioids on
  respiration Baily -91, Jarvis -92
• Reduced postoperative shivering Buggy -97,
  Mao -98
• Reduced PONV Kobayashi -97, Oddby -02
• Reduced salivation and gastric
  secretion Watkins -80, Cheng -87
• - As good as benzodiazepines as
  premedication Grottke -03

11

• CLONIDINE IN ADULT ANAESTHESIA
• Epidural administration
• Enhancement of motor and sensory quality of
  epidural blockade Eisenach -96
• with local anaesthetics
• - Prolonged postoperative pain relief
  alone DeKock -93
• Intrathecal administration
• Prolongation of sensory and motor blockade of
  intrathecal bupivacaine Racle -87, Fogarty -93
• Peripheral nerve blocks
• Prolongation of the duration of brachial plexus
  lock Murphy -00, El Saied -00

12

• CLONIDINE SIDE EFFECTS
• Bradycardia and hypotension average incidence of
  14. Ghignone -86, Stone -88
• Preserved cardiovascular responsiveness,
  responsive
• to anticholinergics, volume substitution and
  inotropes.
• - Prolonged sedation Walland -77
• Reduced salivation, dry mouth Watkins -80,
  Cheng -87
• - Attenuation of rise in blood glucose during
  surgery Joffe -86

13

• CLONIDINE IN PAEDIATRIC ANAESTHESIA
• Oral clonidine 4 mcg/kg provided better
  sedation Mikawa -93
• than diazepam 0.4 mg/kg or clonidine 2 mcg/kg
• Oral clonidine 3 mcg/kg attenuated haemodynamic
  response Ramesh -97
• to endotracheal intubation
• 24 mcg/kg oral clonidine reduces induction dose
  of intravenous Nishina -94
• barbiurate in children 712 years
• - Reduction of PONV after oral and caudal
  clonidine Mikawa -95, Motsch -97
• - Reduced incidense of POV in strabismus
  surgery Mikawa -95, Handa-01

14

• CLONIDINE IN PAEDIATRIC ANAESTHESIA
• Prevention of sevoflurane induced agitation
  after clonidine 3 mcg/kg caudal Bock -02
• or intravenous
• Oral clonidine 4 mcg/kg reduces postoperative
  pain Mikawa -96
• A combination of clonidine and diclofenac or
  flurbiprofen Nishina -00
• improves postoperative analgesia
• Effective treatment of herpes zoster neuralgia
  with clonidine ointment Hagihara -02
• in a 9 year old child
• Ropivacaine with or without clonidine improves
  pediatric tonsillectomy pain Giannoni -0

15
CLONIDINE IN PAEDIATRIC ANAESTHESIA - Clonidine
15 mcg/kg as adjunct to local anaesthetics Jamal
i -94, Lee -94 prolonges and improves
postoperative pain relief Cook -95, Ivani -96
following caudal administration Motsch -97,
Klimscha -98 - Addition of epidural infusion
of clonidine to ropivacaine De Negri 01, Klamt
-03 improves postoperative pain relief -
Clonidine prolongs spinal anesthesia
(bupivacaine) Rochette -04 in
newborns - Epidural clonidine is followed
by less side-effects Cucchiaro -03 and is
less potent than epidural morphine - Further
testing, including large clinical trials, is
Ansermina -03 required before routine use of
nonopioid additives for caudal blockade in
children. Review.
16
SIDE EFFECTS AFTER AXIAL ADMINISTRATION IN
CHILDREN

• Haemodynamic side effects are mild even at
  higher doses Motsch -97
• of clonidine (5mcg/kg)
• - Sedation is significant only at high doses
  (5mcg/kg) Lee -94
• - No contribution to PONV Jamali -94, Lee -94,
  
• 
  
  Motsch -97, Luz -99
• - Apnoea in a term neonate (caudal clonidine
  2mcg/kg) Breschan -99

17

• CLONIDINE ADVERSE EFFECTS, POISONING AND FATAL
  OUTCOME
• - Respiratory depression following massive
  overdose Olson -83, Anderson -81
• - Postoperative apnoea in two preterm infants
  following Breschan -99, Bouchut -01
• caudal clonidine
• - Apnoea in a former preterm infant after caudal
  bupivacaine
• and clonidine for inguinal hernia
  repair Fellmann -03
• - 1000 fold unintentional overdose of clonidine
  caused no
• respiratory depression Romano -01
• - A few cases of sudden unexplained deaths in
  children after

18
Pharmacokinetic data of clonidine after
intravenous administration children vs adults.
19
Blood pressure response in patient no. 1
(harmonic undulation). he solid line indicates a
possible dampened sine wave response.
20
Mean (SD) heart rate response after an
intravenous bolus injection of clonidine mcg
kg-1) in children p 0.006.
21
Plasma pharmacokinetics of rectal clonidine (2.5
mcg kg-1) in children. Data from all patients are
included. Dashed line lowest reported plasma
concentration associated with a clinical effect
in adults (0.2 ng ml-1).
22
RECTAL ADMINISTRATION OF CLONIDINE 2.5
MCG/KG. T 1/2 elimination 12.5
hours Lönnqvist, Bergendahl, Eksborg -94 Time to
Tmax 51 min
Bioavailability 95 .

23
EPIDURAL BOLUS CLONIDINE 2 MCG/KG
A. Clonidine plasma concentration -time
relationship for a patient with a rapid
absorption pattern (patient no. 3). B.
Absorption-time relationship in the same
patient.
24
EPIDURAL BOLUS CLONIDINE 2 MCG/KG
A. Clonidine plasma concentration- time
relationship for a patient with a slow
absorption pattern (patient no. 2). B.
Absorption-time relationship in the same
patient. 0
25
EPIDURAL BOLUS CLONIDINE 2 MCG/KG. T max 48
193 min. Ivani, Bergendahl, Lönnqvist, Eksborg
-98 Time to 95 absorbtion 36 min 7.6 hours.


26
Postoperative sedation (solid line) and
postoperative analgesia (dotted line) in relation
to time. At 9 h postop no patient was scored to
have residual sedation. At 24 h postop 4 patients
still had no need for supplemental analgesia.
27
STRESS RESPONSE AFTER INTUBATION
Percentage change in neuropeptide Y
concentrations compared with baseline (whole
study population).
28
BLOOD PRESSURE VARIABILITY AFTER CONTINOUS
EPIDURAL CLONIDINE INFUSION
Individual systolic blood pressure recordings in
patients receiving a postoperative epidural
infusion of either plain ropivacaine 0.1 (group
R) or a co-infusion of ropivacaine
29
(No Transcript)
30

• Parental preferences of children behaviour during
  the first 24 hours.

31
CLONIDINE VS MIDAZOLAM AS PREMEDICATION IN
CHILDREN UNDERGOING ADENO-TONSILLECTOMY Sum of
sedation score was higher in the
clonidine Bergendahl, Lönnqvist, Eksborg 04.
group compared to midazolam group two hours
postoperative (plt0.001). Sum of
postoperative confusion score was lower in
the
clonidine group compared to midazolam in
children less than 5 years (p0.001). A
higher incidence of confusion in boys compared to

girls in both groups (p0.018). No
shivering in the clonidine group, but shivering
was
observed in 5 patients in the midazolam
group (p0.057) Children in the clonidine group
were more sedated than
children in the midazolam
group 24 h postoperatively.
32
CLONIDINE Advantages Possible
advantages Preoperative sedation Postoperativ
sedation Reduction of anaesthetic
requirements Action of sleep like sedation
Attenuation of haemodynamic response to
Satisfied parents tracheal intubation and
surgical stimuli Decreased incidence of
shivering Reduction of PONV Reduced
postoperative confusion after sevoflurane
anaesthesia Postoperative analgesia Taste les
solution Prolonged effect , when operation is
delayed No effect on respiration no
interaction with opioids.
33
CLONIDINE Possible disadvantages Disadvantage
s Postoperative sedation Higher postoperative
pain scores requirements compared to
midazolam. Attenuation of rise in blood glucose
during surgery Attenuation of HR
response to atropine Late onset of
action after oral and rectal route
34
CLONIDIN SOM PREMEDICINERING TILL
BARN Indikation Premedicinering till ASA I
barn 118 år inför rutinoperationer. Dosering
Clonidin 4 mikrogram per kg kroppsvikt och
Atropin 20 mikrogram per kg kroppsvikt ges oralt
alternativt rektalt ca 1 tim före planerad
anestesistart. Kontraindikationer Hypotension,
hypovolemi. AV block II III. Långt P-R
intervall. Oral premedicinering Beräknad mängd
ges med eller utan saft. Rektal
premedicinering Ges enligt lokal
tradition. Färdigberedd lösning innehåller 40
mikrogram Clonidin per milliliter och 200
mikrogram Atropin per milliliter. Lösningen
doseras enligt lista nedan.
35
Dokumentation Clonidin ( CatapresanR
). Farmakodynamik Clonidin är en alfa-2
agonist med sederande och analgetiska egenskaper.
Begynnande klinisk effekt (sedering) ses oftast
efter ca 10 minuter. Den sederande effekten kan
kvarstå i upp till 24 timmar. Detta bör man
informera föräldrar och barn om. Hos små barn
minskar även den postoperativa konfusionen efter
Sevoflurananestesi. Hos vuxna har man även
konstaterat minskad postoperativ shivering och
illamående-kräkningar. Farmakokinetik Den
rektala biotillgängligheten är ca 95 och maximal
plasmakoncentration uppnås efter 50 min vid
rektal administrering. Halveringstiden är ca 12
timmar. Den orala biotillgängligheten hos barn är
ej känd men hos vuxna är den gt 90.
36
Anestesi Clonidin kan i princip kombineras med
alla typer av rutinanestesi. Man kan förvänta sig
en minskning av blodtrycket med ca 20 i samband
med anestesi och en lindrig och kortvarig nedgång
av hjärtfrekvensen. Därför kombineras Clonidin
alltid med ett antikolinergikum,
Atropin.Allvarligt blodtrycksfall eller
bradycardi under anestesi behandlas enlig lokala
rutiner. Clonidin påverkar ej verkningsmekanismen
av antikolinerga eller inotropa läkemedel.
Clonidin har inga andningsdeprimerande egenskaper
och kan kombineras med alla typer av
opioider. ÖverdoseringToxicitet Säkerheten
för Clonidin är stor och högre doser (gt10 mcg/kg)
ger i stället blodtrycksstegring. En 1000-faldig
överdos hos ett barn gav enligt litteraturen ej
allvarlig påverkan på cirkulation eller andning. 
37
DOSERING AV CLONIDIN-ATROPIN I ML. REKTAL ELLER
ORAL PREMEDICINERING
VIKT KG     ML              VIKT KG    
ML              VIKT KG     ML10               1
.0               20               2.0             
  30               3.0 11               1.1      
         21               2.1               31    
           3.112               1.2              
 22               2.2               32            
   3.2 13               1.3               23     
          2.3               33               3.3
14               1.4               24             
  2.4               34               3.415      
         1.5               25               2.5   
            35               3.516              
 1.6               26               2.6           
    36               3.617               1.7    
           27               2.7               37  
             3.718               1.8            
   28               2.8               38          
     3.819               1.9               29   
            2.9               39   
           3.9


40
4.0
45
4.5


gt50 kg ges 5.0 ml.
H. Bergendahl Öl. Med Dr (Nyköpings
Lasarett)  Huddinge Universitetssjukhus, Smärtavde
lningen, 08/58580000.PA Lönngvist
Verksamhetschef, Doc   Astrid Lindgrens
Barnsjukhus, KS.   
38
(No Transcript)