1 / 38

Clonidine in Paediatric Anaesthesia

Clonidine in Paediatric Anaesthesia. MD PhD Henrik Bergendahl Smärtavdelningen, Anestesikliniken, Karolinska Universitetssjukhuset. c Bergendahl.

lamar
Download Presentation

Clonidine in Paediatric Anaesthesia

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Clonidine in Paediatric Anaesthesia MD PhD Henrik Bergendahl Smärtavdelningen, Anestesikliniken, Karolinska Universitetssjukhuset

  2. c Bergendahl Inhibitory and excitatory adrenergic neurones. McCaughey W, Anaeshetic Physiology and Pharmacology, Churchill Livingstone, modified with permission.

  3. c Bergendahl Sites of heamodynamic action of alpha-2 adrenoceptor agonists. (Eisenach 1996; with permission.)

  4. c Bergendahl Sensory cortex, thalamus Limbic system Hypothalamus Relay regions NTS RVLM IML column Symathetic nerve terminals Adrenal medulla • Mode of action of antihypertensives. (Prichard 2000; with permission).

  5. c Bergendahl Non-selective alpha-2 adrenoceptor agonists Noradrenaline Adrenaline Selective alpha-2 adrenoceptor agonists Dexmedetomidine Mivazerol Clonidine Alfa-Methyldopa • Selective and nonselective alpha-2 adrenoceptoragonists. (Khan 1999; with permission).

  6. c Bergendahl

  7. c Bergendahl • A comparison of commonly used preanaesthetics and clonidine. • (Halldin-Lindahl, Anestesi, Liber AB, modified with permission.)

  8. c Bergendahl • 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

  9. c Bergendahl • 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

  10. c Bergendahl • 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 • in combination with local anaesthetics • IVRA • - Improves postoperative analgesia as adjunct to IVRA Choyce -02

  11. c Bergendahl • 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 • - Risk of awareness (reduced anaesthetic requirements) Clementy -86

  12. c Bergendahl • 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 • 2–4 mcg/kg oral clonidine reduces induction dose of intravenous Nishina -94 • barbiurate in children 7–12 years • - Reduction of PONV after oral and caudal clonidine Mikawa -95, Motsch -97 • - Reduced incidense of POV in strabismus surgery Mikawa -95, Handa-01 • - No effect on POV after oral clonidine 4 mcg/kg Gulhas -03

  13. c Bergendahl • 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 • Children premedicated with oral clonidine 4 mcg/kg had higher pain scores • compared to oral midazolam after tonsillectomy. Fasi-01

  14. c Bergendahl CLONIDINE IN PAEDIATRIC ANAESTHESIA - Clonidine 1–5 mcg/kg as adjunct to local anaesthetics Jamali -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.

  15. c Bergendahl 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

  16. c Bergendahl • 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 • clonidine in combination with other drugs Maloney -95 • 10 060 exposures of clonidine in children with 6042 symptomatic Klein-Schwartz -02 • children lethargy 80% bradycardia 17% hypotension 15% • respiratory depression 5% • 1 fatality in a 23 month old. • Serious toxic effects and death can occur

  17. c Bergendahl • Pharmacokinetic data of clonidine after intravenous administration: children vs adults.

  18. c Bergendahl • Blood pressure response in patient no. 1 (harmonic undulation). • he solid line indicates a possible dampened sine wave response.

  19. c Bergendahl • Mean (SD) heart rate response after an intravenous bolus injection of clonidine mcg kg-1) in children; ** p = 0.006.

  20. c Bergendahl • 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).

  21. 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 %. “ “ “

  22. c Bergendahl 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.

  23. c Bergendahl 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

  24. 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. “ “ “ “

  25. c Bergendahl • 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.

  26. c Bergendahl STRESS RESPONSE AFTER INTUBATION • Percentage change in neuropeptide Y concentrations compared with baseline (whole study population).

  27. c Bergendahl 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

  28. c Bergendahl

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

  30. 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 (p<0.001). Sum of postoperative confusion score was lower in “ “ “ the clonidine group compared to midazolam in children less than 5 years (p=0.001). A higher incidence of confusion in boys compared to “ “ “ girls in both groups (p=0.018). No shivering in the clonidine group, but shivering was “ “ “ observed in 5 patients in the midazolam group (p=0.057) Children in the clonidine group were more sedated than “ “ “ children in the midazolam group 24 h postoperatively.

  31. 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.

  32. CLONIDINE: • Possible disadvantages Disadvantages • 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

  33. c Bergendahl CLONIDIN SOM PREMEDICINERING TILL BARN Indikation:Premedicinering till ASA I barn 1–18 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.

  34. c Bergendahl 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 > 90%.

  35. 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. Överdosering–Toxicitet: Säkerheten för Clonidin är stor och högre doser (>10 mcg/kg) ger i stället blodtrycksstegring. En 1000-faldig överdos hos ett barn gav enligt litteraturen ej allvarlig påverkan på cirkulation eller andning.

  36. c Bergendahl 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               3.314               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 >50 kg ges 5.0 ml. H. Bergendahl Öl. Med Dr(Nyköpings Lasarett)  Huddinge Universitetssjukhus, Smärtavdelningen, 08/58580000.PA Lönngvist Verksamhetschef, Doc Astrid Lindgrens Barnsjukhus, KS.

  37. c Bergendahl

More Related