1、Remifentanil PCA labor analgesia:applications and concerns瑞芬分娩镇痛的运用和问题lRemifentanil is an opioid with an ESTER bond l(other common esters in anesthesia)succinylcholine esmolollRemifentanil is metabolized by nonspecific esterases in blood and tissue(mostly gut)lThe placenta is full of esterases Nearl
2、y fully developed at time of birthExtremely rapid onsetExtremely rapid offsetLimited variability between individual patientsMinutes since bolus injection0246810Percent of peak effect site opioid concentration020406080100fentanylsufentanilalfentanilremifentanilMinto et al,Anesthesiology 86:10-23,1997
3、Minutes since bolus injection0246810Percent of peak effect site opioid concentration020406080100remifentanilMinto et al,Anesthesiology 86:10-23,1997-Rapid onset of bolus dose allows for anticipation of contraction-Often peak analgesic effect lags behind peak of contraction Extremely rapid offset(hal
4、f life 3-4 minutes)Not influenced by:Hepatic diseaseRenal diseasePseudocholinesterase deficiencyAdministration of neostigmineVery young age(fetus)Expected plasma concentration following bolus of 1 unitAge range:20-85 yrs Very rapid decrease Less variability than with other anesthetic drugs and opioi
5、dsUnit dispostion functionTime(minutes)0601201802400.0000010.000010.00010.0010.010.1010200.0010.010.1Minto et al,Anesthesiology 86:10-23,19970.1110100060120180240300360420480Minutes Concentration(ng/ml)Glass et al,Anesth Analg 77:1031-1040,1993Minutes since bolus injection0120240360480600Percent of
6、peak plasmaopioid concentration0.1110100fentanylsufentanilalfentanilremifentanilMinto et al,Anesthesiology 86:10-23,1997Glass et al,Anesth Analg 77:1031-1040,199320406080100120140-300306090120150180210240270Minutes Minute Ventilation(percent of baseline)Recovery from remifentanil is unlike that seen
7、 with any other opioid The time to a given decrease in effect site concentration is constant over time of infusion no accumulation0204060Minutes required for a given percent decrease in effect site concentration0306090120Minutes since beginning of infusion012024036048060006012018024030020%decrease50
8、%decrease80%decreasefentanylfentanylfentanylalfentanilalfentanilalfentanilsufentanilsufentanilsufentanilremifentanilremifentanilremifentanilMinto et al,Anesthesiology 86:10-23,1997 Check out your pump as thoroughly as you check out your anesthesia machine.Is your drug dilution correct?Is the syringe
9、 adequately held?Is the syringe plunger properly held in the clamp?Are your infusion units correct?Is the weight correct(for calculator pumps)?Has the dead space been taken out of the line?Have the batteries been checked?Many complications are due to concentration and pump errors.Infuse as close to
10、the IV catheter site as possible.Typical IV tubing contains 3-5 mls of dead space between injection ports and catheter.Remifentanil 70 mg(1 mg/kg)Fentanyl 225 mg(3.2 mg/kg)Alfentanil 1000 mg(15 mg/kg)Sufentanil 25 mg(0.35 mg/kg)Remifentanil 35 mg(0.5 mg/kg)Fentanyl 100 mg(1.5 mg/kg)Alfentanil 500 mg
11、(7 mg/kg)Sufentanil 12 mg(0.2 mg/kg)Concentrations rapidly rise during infusions.With infusions,expect apnea and rigidity within 2-3 minutes.Especially at a rate of 1.0 mg/kg/minLower bolus doses and/or infusion rates are required for labor analgesia.05101520250246810MinutesRemifentanil concentratio
12、n(ng/ml)1.0 mg/kg/min1 mg/kg bolusApneaVentilatory DepressionRigidity0.5 mg/kg/min 0.2 mg/kg/min Apnea likely 0.1 mg/kg/min Respiratory depression 0.05 mg/kg/min Little likelihood of respiratory depression 0.025 mg/kg/min Few problems expected Modestly analgesic02468100102030405060MinutesRemifentani
13、l concentration(ng/ml)0.1 mg/kg/min0.025 mg/kg/minRespiratory depressionApneaRigidity0.05 mg/kg/min0.2 mg/kg/minAnalgesialCan be used as patient controlled analgesia lCan be used as an infusionlLimited reports of success with both patient controlled analgesia and a background infusion Multiple case
14、reports of respiratory depression However one large retrospective trial from Shanghai with good results will be discussed in detail.lRegional is still king!lNot everybody is eligible At Columbia University in New York,approximately 90%of women who deliver vaginally have epidural analgesia.At Stanfor
15、d University,80%have epidural analgesia Nearly 100%want analgesia.lContraindications:Anticoagulation SepsisNeurological DiseasesNeedle phobia-not everybody wants a needle stuck in her backlProtocol:Bolus 0.4 mg/kg-lockout 1 minute-or 50%nitrouslRemifentanil group-VAS scores were reduced from 7 to 4.
16、5.lNitrous group-VAS scores not significantly differentlRemifentanil group was more sedatedlProtocol:Bolus Remifentanil 40 mg-lockout 2 minute-or Pethidine(meperidine)15mg-lockout 10 minuteslVAS scores were not different(6.4 vs.6.9)lWomen strongly preferred remifentanillRemifentanil group was more s
17、edatedlLin R,Tao Y,Yu Y,Xu Z,Su J,and Liu Z.Intravenous Remifentanil versus Epidural Ropivacaine with Sufentanil for Labour Analgesia:A Retrospective Study.PLoS One.2014;9(11)l200 epidurals:170 remifentanillCombined infusion 0.04-0.05 mcg.kg/min with option for PCA bolus of 0.4 mcg/kg q 5 minutes.lA
18、ll parturients had supplemental oxygen and 1:1 supervisonlNo difference in APGARSlMost infants did fine in both groupslLower Umbilical artery and vein pHlNumber required resuscitation not reportedl%umbilical vein less than 7.2 not reported Maternal desaturation and sedation common,particularly with
19、onset.Absolutely requires supplemental oxygen and 1:1 supervision Cannot be administered epidurally or intrathecally.Contains glycine.Benefits:Rapid onsetRapid offset,rapid recoveryHighly predictableProvides some analgesia when epidural is contraindicatedRisks:Very modest increase in costRequires expert set up and titrating Requires continued 1:1 supervision
