The combination of low dose of na by liaoxiuli

VIEWS: 21 PAGES: 45

									The combination of low dose
of naloxone and morphine in
PCA
10/4 Morning Meeting
Yu Chang Yeh
The combination of low dose of
naloxone and morphine in PCA
  Objective
  Backgrounds
  Patient selection and exclusion
  Standard setup
The combination of low dose of
naloxone and morphine in PCA

  Intolerable side effects
  Low side effects setup
  Treatment failure and withdrawal
  Relevant studies
Objective
  Dose the combination of low does
  naloxone and morphine in PCA reduce
  the incidence of side effects and
  requirement of morphine?
Backgrounds 1
  Without antiemetic drugs, the incidence of
  nausea was on average 43%, of vomiting
  was 55%, and of any emetic event was
  67%.(1)
  Tramer MR, Walder B. Efficacy and adverse
  effects of prophylactic antiemetics during
  patient-controlled analgesia therapy: a
  quantitative systematic review. Anesth Analg
  1999;88:1354-61
Backgrounds 2
  Pruritus 55%
  Gan TJ, Ginsberg B, Glass PS, Fortney J,
  Jhaveri R, Perno R. Opioid-sparing
  effects of a low-dose infusion of
  naloxone in patient-administered
  morphine sulfate. Anesthesiology
  1997;81:77-84
Backgrounds 3
  Low dose naloxone infusion
  (0.25ug/kg/hr) was effective in
  reducing the incidence of nausea,
  vomiting, and pruritus. It also deceased
  opioid requirements.
  Placebo/ 0.25ug/kg/hr/ 1ug/kg/hr
  20/20/20 --- total 60
  Gan Anesthesiology 1997;81:77-84
Backgrounds 4
  1ug/kg/hr decreases opioid-related side
  effects but seemed to attenuate the
  pain relief provided by morphine.
  64.7+/- 33mg vs 59.1 +/- 27.4mg in
  Placebo
  Gan Anesthesiology 1997;81:77-84
  Included in Miller Anesthesia
Backgrounds 5
  In animal study
  Enhanced release of endogenous opiates
  Up-regulation phenomenon
  Within 30 min
  Paronis CA J Pharmaol Exp Ther
  1991;259:582-9.
  Yoburn BC J Pharmaol Exp Ther 1986;239:
  132-5.
Backgrounds 6 But……
 Direct combination of naloxone and
 morphine in PCA does not decrease
 opioid requirements or morphine-
 related side effects in the postoperative
 period.
 Cepeda MS, Africano JM, Manrique AM,
 Fragoso W, Carr DB. Pain 2002;96:73-
 79
Backgrounds 7
  Systemic reviews suggest that prophylaxis
  does not work very well, that there is a finite
  risk of adverse drug reactions with most
  antiemetic intervention, ant the treatment
  may be more cost effective than prophylaxis.
  Tramer MR. A rational approach to the
  control of postoperative nausea and vomiting:
  Acta Anesth Scand 2001;45:14-19
Backgrounds 8
  We try to find out an optimal
  combination ratio of naloxone and
  morphine in PCA to reduce the severity
  of side effects related with PCA
  morphine.
  Only patients suffered form intolerable
  side effects were enrolled in our study.
                                              <Inclusion criteria >
                                  1. Age 18-65y/o
                                  2. ASA I – III
                                  3. Surgical procedure < 4hours




Tab 1
        <Exclusion   criteria >
        1. Intraoperative
        Fentanyl use > 4μg/kg
        2. Post-OP NSAIDs                  <Standard PCA Setup>
        and antiemetics use                Drug: 1mg/ml Morphine
                                           PCA dose: 2ml
                                           Lockout time 10min


                                                                            NO



                                          Intolerable side effects
                                          A. Nausea / V omiting
                                          B. Pruritus
                                          C. Urinary retention
                                          D. Change in consciousness
                                          E. Respiratory depression




                                                      Yes


                                            <Adjust PCA Setup>
                                            Drug:1mg/ml Morphine+ 2μg/ml
                                            Naloxone
                                            PCA dose: 2ml
                                            Lockout time 10min



                                                                           NO




                                          Intolerable side effects
                                          A. Nausea / V  omiting
                                          B. Pruritus
                                          C. Urinary retention
                                          D. Change in consciousness
                                          E. Respiratory depression
                                          F. Increase intensity of pain




                                                      Yes


                                   1. Withdrawal
                                   2. Adjunct drugs for side effects
Patients selection
    Inclusion criteria
  1. Age 18-65y/o
  2. ASA I-III
  3. Surgical procedure < 5 hrs
  4. Use PCA for postoperative pain
  control
  5. Who suffers form intolerable side
  effects
Patient exclusion
1. Intraoperative Fentanyl use 4μg/kg
2. Patient with hiatal hernia and
  esophageal reflux symptoms
3. Recent use of antiemetics or
  antipruritic treatment after
4. Recent use of NSAIDs after operation
Standard PCA Setup
  Morphine 1mg/ml
  PCA dose 2ml
  Lockout time 10min
  No continuous dose
Intolerable side effects
  Nausea and vomiting
  Pruritus
  Urinary retention
  Change in consciousness
  Respiratory depression
Low side effect PCA setup
  PCA
  Morphine 1mg/ml
  Naloxone 2μg/ml
  PCA dose 2ml
  Lockout time 10min
  No continuous dose
Treatment failure
  Nausea and vomiting
  Pruritus
  Urinary retention
  Change in consciousness
  Respiratory depression
  Increase intensity of pain
Withdrawal
  Withdrawal
  Adjunct drugs for side effects
Measurements and Evaluation
  Evaluation of Pain intensity
     Pain on exertion – verbal numerical scale
      0-10
     Pain at rest – verbal numerical scale 0-10
Measurements and Evaluation
  Evaluation of side effects
     Nausea –
        0 absent
        1 mild
        2 moderate
        3 severe
     Vomiting –
        number of events
Measurements and Evaluation
  Pruritus –
     0   absent
     1   mild
     2   moderate
     3   severe
  Urinary retention –
     yes / no
Measurements and Evaluation
  Consciousness –
     0   alert
     1   sleepy
     2   stupor
     3   coma
  Respiratory depression –
     respiratory rate
        個案編號:
               Low Dose Naloxone in PCA 研究記錄表
        姓名                        性別           (   )M (   )F   病歷號




Tab 2
        Age                 y/o   身高                      cm 體重             kg
        ASA                       手術日期                         手術時間
        過去病史 (   ) HT ( )DM ( ) CVA ( ) CAD ( ) Allergy
             (   ) Asthma ( )COPD ( ) Prior Surgery _______
             (   ) Others
        手術名稱


        麻醉方式 (    )ETGA (    )LMA (    ) IVG


                 術中使用 Fentanyl 總劑量 ______ug / kg
        Time                        靜痛 動痛 BP HR RR             噁心 嘔吐 癢   積尿 意識
              PCA 開始使用時間
              發生副作用時間
              改成研究配方時間
              Demand Delivery Total
        10min
        30min
        1hr
        2hr
        4hr
        8hr

        發生副作用前使用 PCA 總劑量 ____ mg
        整個療程 PCA 用量 ____ mg
        評估指數參考依據 (請填數字或文字敘述亦可)
        休息時疼痛               疼痛指標 0-10 0 不痛 10 最痛
        移動時疼痛               疼痛指標 0-10 0 不痛 10 最痛
        生命徵象                血壓 心跳速率 呼吸速率
        意識變化                0 清醒 1 想睡 2 沉睡 3 昏迷
        噁心                  0 無 1 輕微 2 中等 3 嚴重
        嘔吐                  請記錄次數
        皮膚癢                 0 無 1 輕微 2 中等 3 嚴重
        尿液積留                0 無 1 有
              Low Dose Naloxone in PCA 研究記錄表
        姓名                          病歷號


Tab 3   開始使用 PCA 時間
        產生副作用時間
                                       月
                                       月
                                                  日
                                                  日
                                                           時
                                                           時
                                                               分
                                                               分
        產生副作用時評估
        靜痛    動痛   BP   HR     RR    意識    噁心         嘔吐   癢   積尿


        改成低副作用配方後一小時評估
        靜痛    動痛   BP   HR     RR    意識    噁心         嘔吐   癢   積尿


        兩小時後評估
        靜痛    動痛   BP   HR     RR    意識    噁心         嘔吐   癢   積尿


        四小時後評估
        靜痛    動痛   BP   HR     RR    意識    噁心         嘔吐   癢   積尿


        八小時後評估
        靜痛    動痛   BP   HR     RR    意識    噁心         嘔吐   癢   積尿


        評估指數參考依據 (請填數字或文字敘述亦可)
        休息時疼痛                疼痛指標 0-10 0 不痛 10 最痛
        移動時疼痛                疼痛指標 0-10 0 不痛 10 最痛
        生命徵象                 血壓 心跳速率 呼吸速率
        意識變化                 0 清醒 1 想睡 2 沉睡 3 昏迷
        噁心                   0 無 1 輕微 2 中等 3 嚴重
        嘔吐                   請記錄次數
        皮膚癢                  0 無 1 輕微 2 中等 3 嚴重
        尿液積留                 0無1有
                             TABLE 10–3. Characteristics of Opioid Receptors

                                                                                         



Tab 4
        Tissue bioassay       Guinea pig ileum       Mouse vas deferens      Rabbit vas deferens

        Endogenous ligand     Enkephalin             Enkephalin              Dynorphin

                              -Endorphin (?)

        Exogenous agonist
                              Morphine               DPDPE                   U 50,488
          ligand

                              Phenylpiperidines      DADLE 1                 Butorphanol

                              DAMGO, DAGO            Deltorphin              Bremazocine

        Antagonist            Naloxone               Naloxone                Naloxone

                              Naltrexone             Naltrindole             NorBNI

        Cloned (human)        Yes                    Yes                     Yes

        Subtypes              1,2,3                  1,2,3                   1,2,3

        G protein–coupled     Yes                    Yes                     Yes

        Adenylate cyclase     Inhibits               Inhibits                Inhibits

        Voltage-dependent
                              Inactivates            Inactivates             Inactivates
          calcium channels

        Potassium channel
                              Increases              Increases               ?
          conductance

                              Analgesia, sedation,
                                respiratory                                  Spinal analgesia
                                depression, miosis,  Supraspinal analgesia     Diuresis
        Actions                 bradycardia, nausea,   Respiratory             Dysphoria
                                vomiting, decreased    depression (?)          Respiratory
                                gastrointestinal                               depression, (weak)
                                mobility
Fig 1
Fig 2
Tab 5
        TABLE 10–22. Reported Severe Complications Following Naloxone Administration

                        NALOXONE DOSE
     AUTHOR                                                   COMPLICATION
                            (IV, mg)

  Azar1068             0.4              Hypertension (270/140)
         1069
  Estilo               0.4              Hypertension (260/140); cerebrovascular accident
           1070
  Flacke               0.4              Pulmonary edema

  Tanaka1071           0.4              Hypertension (340/150)
              1072
  Andree               0.4              Cardiac arrest, death

                       0.4              Cardiac arrest, death
              1073
  Prough               0.1              Pulmonary edema

                       0.2 (+0.3 IM)    Pulmonary edema
                1074
  Michaelis            0.1              Ventricular tachycardia, ventricular fibrillation

                       0.4              Ventricular fibrillation

  Partridge1075        0.08             Pulmonary edema

  Taff 1076            0.3              Pulmonary edema
Relevant Studies 1
  Naloxone – other applications 1
     Septic and hemorrhagic shock
     Alcoholism
     Poatanesthetic apnea in infants
     Primary apnea and periodic breathing
      associated with hypoxemia
     Restore flow-resistive load compensation in
      patients with COPD
Relevant Studies 2
  Naloxone – other applications 2
     May ameliorate the neurologic deficit
      following an ischemic or traumatic
      neurologic insults in animals
Relevant Studies 3
  Other Opioid antagonist
     Naltrexone
     Nalmefene
        Long acting
        Equipotent to naloxone
        Plasma half life 3-10hours
        Naloxone 64 +/- 12min
        Morphine 2-7hours
Relevant Studies 4
  Effects of prophylactic nalmefene on
  the incidence of morphine-related side
  effects in patients receiving intravenous
  PCA
  Saline/ 15ug nalmefene / 25ug
  nalmefene
  Decrease the need for antiemetics and
  antipruritic medications
Relevant Studies 5
  Lidocaine+Morphine vs Morphine alone
  Music
  Men and women
  Naloxone vs PCEA
Relevant Studies 6
  1999 systemic review
     Droperidol
     Clonidine
     Ondansetron
     Tropisetron
     Metoclopramide
     Hyoscine
     Promethazine
Relevant Studies 7
  2000 British Journal of Anesthesia
  Prevention of postoperative nausea and
  vomiting by continuous infusion of
  subhypnotic propofol in female patients
  receiving intravenous PCA
  Placebo, 5, 10, 15, 20 ug/kg/min
  No symptoms
  25%,40%,45%,65%,75%
Relevant Studies 8
  Total fentanyl consumption
  Placebo, 5, 10, 15, 20 ug/kg/min
  413/585/537/514/712 ug
Thanks for your attention!
Have a nice day! 
Sample size
  Null hypothese / one or two sided
  alternative hypothese
  Appropriate statistical test
  Choose a reasonable effect size (and
  variability if necessary)
  Set α,β
  Use the appropriate tables or formula
Tab 6
                 Outcome variables
                 Dichotomous         Continusous

Predictor variable Chi-square test T-test
Dichotomous

                 T-test              Correlation
Continuous                           coefficient
E/S
  Effect Size (E)
     The difference in the mean value of the
      outcome variable between the study group
  Standard deviation(S)
     The variability of the outcome variables
  Standard effective size (E/S)
     For most study 0.1-0.5
Example
 The efficacy of Salbutamol and
 ipratropium bromide for the treatment
 of asthma
 FEV1 after 1 week treatment
 Previous study Mean 2liter with S 1liter
 Effective size 0.2liter (10%)
 Standard effective size 0.2/1 = 0.2
Example
 α= 0.05
 β= 0.2 (power = 0.8)
 Look across the Table
     394 for each group
Example
 Sample size (per equal-sized group)
     = 16 / (E/S)2
 Try to reduce the sample size
     Increase E
     Decrease S

								
To top