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Vasopressin Don't Squeeze Too Tight - Cardiothoracic Symposium

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Vasopressin Don't Squeeze Too Tight - Cardiothoracic Symposium Powered By Docstoc
					     Vasopressin :
don’t squeeze too tight

        Pascal Colson
      Montpellier, France
             Phe3
                                   Vasopressin :
  Tyr2
                    Gln4         Natural compound
Cys1
       S       Asn5
        S
            Cys6                   Functional coupling
 Pro7

       Arg8
               Gly9 NH2
                                   H                      cAMP

                           V2      R     as   AC
                                                         ATP



                                                          IP3, Ca2+
                                   H
                           V1a                            DAG, PKC
                           V1b
                                   R   aq/11 PLC

                                                         PIP2
                                          V1b
Vasoconstriction    Insuline                      Glycogenolysis
                   secretion
     V1a                                              V1a


                                Phe3
   Water             Tyr2
                                       Gln4
reabsorption       Cys1
    ADH                   S
                           S
                                  Asn5
                                                            …?
                               Cys6
         V2         Pro7
                                                 V1a V1b
                          Arg8
                                  Gly9 NH2

   Catecholamine
    and steroid                                   ACTH
     secretion     V1a                          secretion
        V1a V1b                Coagulation      V1b
          Phe3
  Tyr2
                Gln4

                        Vessels
Cys1
AsnS
  S5
         Cys6
 Pro7
   Arg8 Gly9NH
               2




   Flow                Resistance




                       MAP=SVR x CO




                       Blood pressure
                 Integrative physiology

Blood pressure
                  NAS
                  Hormones
                  Angiotensin
                   Vasopressin




                                Normovolemia


                                 TBV
                  Integrative physiology

Blood pressure             1- Vasoconstriction(all)
                           2- Volemia (AII, AVP)



                       2

                   1
                                  Normovolemia


        Volemia decrease            TBV
                 Vasopressin :
   Contribution to cardiovascular regulation

• Hormonal systems (AII, VP) involved :
   • In case of serious cardiovascular failure
     (haemorrhage > 30%)
   • In case of autonomic nervous system impairment
     (anaesthesia)


• Vasopressin :
   • Backup system
   • Arterial vasoconstriction (mesenteric)
                                          Vasopressin :
             Phe3
                                       Synthetic compounds
  Tyr2
                    Gln4
Cys1
       S           Asn5
                                  LVP
        S
            Cys6
 Pro7                                   Phe3
                             Tyr2
       Arg8                                    Gln4
               Gly9 NH2
                           Cys1
                                  S           Asn5
                                   S
                                       Cys6
       AVP                  Pro7                                    Terlipressin
                                  Lys8 Gly9 NH
                                               2
                                                                                        Phe3
                                                                             Tyr2
                                                                                               Gln4
                                                                           Cys1
                                                                                  S       Asn5
                                                                                   S
                                                                    Gly9               Cys6
                                                             Gly9           Pro7

                                                      Gly9                        Lys8 Gly9 NH
                                                                                               2
                               Terlipressin


                     Phe3
              Tyr2
                       Gln4
           Cys1
       Gly9
                S
                S
                      Asn5
                    Cys6
                                    Terlipressin
   Gly9       Pro7            LVP
Gly9            Lys8 Gly9 2
                        NH




                Phe3
           Tyr2                            1       2   3   H
                  Gln4
          Cys1
            S
             S
                 Asn5
               Cys6
           Pro7
              Lys8 NH2
                 Gly9
      Teatment with vasopressin analogs

• Intensive care
    Rescue vasopressor (catecholamine resistance)
    Substitutive treatment (vasopressin deficiency)


• Anesthesia
    Anesthesia induced-hypotension
    Intractable hypotension?
     Post-cardiac surgery vasodilatatory shock


1.   Mean arterial pressure MAP < 70 mm Hg
2. Cardiac index CI > 2.5 L/min/m2 (LVAD)
3. Norepinephrine dependence (norepinephrine > 8 μg/min)
                                          Argenziano et al Circulation. 1997


1.   Mean arterial pressure MAP < 70 mm Hg,
2. Cardiac index CI > 2.5 L/min/m2
3. Norepinephrine dependence (norepinephrine : 14.4±13.7 μg/min)
                            Argenziano et al, J Thorac Cardiovasc Surg 1998

                   Incidence : 10 to 15%
 Post-cardiac surgery vasodilatatory shock


                 MAP         CI              SVR             NE


                             ?
Morales et al,
                 < 60     “Despite                        11.7±13.0
 Ann Thorac                                   -
 Surg 2000       mmHg      LVAD                             μg/min
                        implantation”

Dünser et al
                 < 70       2.5                            1.5±1.5
Anesth Analg                                  -
                 mmHg     L/min/m2                         μg/kg/min
   2001

 Jochberger
    et al
                 < 60                      <1,200          0.1-0.6
  Intensive                  -
                 mmHg                   dyne.s.cm-5.m-2    μg/kg/min
  Care Med
    2009
 Post-cardiac surgery vasodilatatory shock

   Catecholamine dependance, resistance ?

                                                      End organ
           MAP         CI        SVR     Treatment
                                                      perfusion

                                          Inotrope
         MAP < 60     > 2.5
PCSVS      mmHg      L/min/m2
                                 Low     Assistance      
                                            + NE


Septic   MAP < 65     > 3.5                 NE
                                 Low                     
shock      mmHg      L/min/m2           ± Inotrope


     PCSVS : Post-cardiac surgery vasodilatation shock
        Catecholamine resistance ?

    Argenziano 1997      NE <0.5 mg/h
P   Argenziano 1998   NE 0.05 to 1.7mg/h
C
S    Morales 2000     NE < 0.05 - 1.5mg/h
V
S     Dünser 2001      NE <0.5 - 15mg/h
    Jochberger 2009   NE <0.5 – 2.5mg/h
      Septic shock    NE 0.15 – 2.3 mg/h



                       Russel et al N Engl J Med 2008
                 Vasopressin deficiency
    Landry, Circulation 1997
                                 Argenziano, J Thorac Cardiovasc Surg 1998



Depletion of endogenous
  AVP stores following
 vigorous stimulation of
  AVP release from the
    neurohypophysis

                        Vasopressin treatment :
                        • 0.01 U/min provides about 30 pg/mL
                        • 0.04 U/min provides about 100 pg/mL
            Vasopressin in septic shock


778 patients
NorE 5 μg/min
396 VP ; 382 norE
VP 0.01 to 0.03U/min *
NorE 5 to 15 μg/min *
* target MAP

Mortality       Vasopressin       Norepinephrine            P
28-day          35.4%             39.3%                     0.27
90-day          43.9%             49.6%                     0.10


            James A. Russell, for the VASST Investigators
                   N Engl J Med 2008;358:877-87
Vasopressin and post CS vasodilatation

        Vasopressin deficiency?
                      Depletion of endogenous
     AVP pg/mL          AVP stores following
                           Copeptin pg/mL
                     chronic stimulation of AVP
                      release from the neuro-
                             hypophysis ?



                                    *         *



          CTL                                 PCSVS
          P Colson, Crit Care 2011; 15:R255
                              Pre-pro-AVP
Nt   SIGNAL        AVP        NEUROPHYSIN II              COPEPTIN         Ct



 1            20         28                     124                  164




         Crit Care Med 2009


                                            J Am Coll Cardiol 2008
   Vasopressin and post CS vasodilatation

             Vasopressin deficiency?

Studies      Number      Risk factors
JCTVS,1998   40          OHT, LVAD, Low LVEF, ACEI
ATS,2000     50          LVAD implantation
JCTVA,1998   9           Severe heart failure




                         Heart failure, low EF
   Vasopressin and post CS vasodilatation

                 Vasopressin treatment
             Retrospective not controlled studies

Studies         Number Indication      Dose (U/min)   Mortality
JCTVS,1998      40      LVAD/OHT       0.01           7.5%
JCTVA,1998      3       Post CPB       0.04-0.33      66%
ATS,2000        50      LVAD           0.09±0.05      26%(?)
AA,2001         25      Post CPB       0.07-0.10      56%
ICVTS,2007      9       Post CPB+PH    0.05-0.10      22%

          Vasopressin treatment :
          • 0.01 U/min provide about 30 pg/mL
          • 0.04 U/min provide about 100 pg/mL
          [0.01 to 0.33 U/min  30 to >1000 pg/ml]
         Vasopressin in vasodilatory shock


50 patients
NorE 0.6 μg/kg/min for
vasodilatory shock due to
sepsis, SIRS or after
cardiac surgery
VP 0.033 or 0.067 U/min

                            ICU Mortality
          Vasopressin       0.033 U/min      0.067 U/min   P
                            52%              52%           1


                        Christian Torgersen et al,
                   Intensive Care Med (2010) 36:57–65
          Phe3
  Tyr2
                Gln4

                        Vessels
Cys1
AsnS
  S5
         Cys6
 Pro7
   Arg8 Gly9NH
               2




   Flow                Resistance
         Phe3
  Tyr2
             Gln4
Cys1
   S
   S
            Asn5
         Cys6
 Pro7
   Arg8 Gly9NH
               2
          Phe3
  Tyr2
                Gln4

                        Vessels
Cys1
AsnS
  S5
         Cys6
 Pro7
   Arg8 Gly9NH
               2




   Flow                Resistance




                       Gut ischemia
              Vasopressin : Gut ischemia




                                   Vasopressin treatment
                                     0.01 to 0.33 U/min 
                                      30 to >1000 pg/ml
                                    6 to 200 times normal!!!
      Am J Physiol 289:168, 2005

[O]VP .03 U/min)
Vasopressin : Gut ischemia
          Phe3
  Tyr2
                Gln4

                        Vessels
Cys1
AsnS
  S5
         Cys6
 Pro7
   Arg8 Gly9NH
               2




   Flow                Resistance
          Phe3
  Tyr2
                Gln4

                        Vessels
Cys1
AsnS
  S5
         Cys6
 Pro7
   Arg8 Gly9NH
               2




   Flow                Resistance
              Terlipressine Glypressine®


Gp 1 : NE

Gp 2 : NE
+ terlipressine 1mg

Gp 3 : NE
+ terlipressin + dobu 20µ




                            Anesthesiology 2008
Vasopressin : preventive treatment?




                                       VP 0.03 U/min




Hypotensive episodes   4±2 vs 1±1
Intubation time        1.0±0.4 d vs 1.4±0.5 d
Lactate                ????
Vasopressin : preventive treatment?




                             46 patients
                 Gp A Ramipril wd 1d
                 Gp B Ramipril till OD
                 Gp C Ramipril + AVP (0.03 U/min)

                           Lactate ????




               JCVA 2009
          Vasopressin treatment

• VP physiology :
  • Backup system
  • Strong mesenteric vasoconstrictor
     Vasopressin treatment :
     • 0.01 U/min provides about 30 pg/mL
    PHARMA [E] COLOGY
     • 0.04 U/min provides about 100 pg/mL
     •> 0.10 U/min, in ICU :
• VP treatmentshould be avoided
   • Backup treatment, used cautiously :
      • Monitoring of VP deficiency (Copeptin?)
      • Lower dose as possible
      • Shorter time as possible
Thank you for your attention
RASa, perioperative instability?
… or propofol induced instability?
                2,5
                                       Rats : WKY                  2,5
                                                                                    Rats : SHR
                  2                                                 2


Noradrenaline   1,5                                                1,5


 ± Propofol       1                                                 1

                0,5                                                0,5

                  0                                                 0
                          -10    -9         -8    -7     -6   -5         -10   -9    -8         -7    -6   -5
                                        WKY           WKYp                           SHR         SHRp


                      3                                             3

                 2,5                                               2,5

                      2                                             2
 Vasopressin     1,5                                               1,5

  ± Propofol          1                                             1

                 0,5                                               0,5

                      0                                             0
                           -11        -10        -9     -8    -7         -11   -10         -9        -8    -7
                                        WKY            WKYp                          SHR         SHRp




                Boillot et al, Br J Anaesth 83:622-9, 1999
Vasopressin increase with low CO




                  r =0.36, p <0.01
   Nakamura et al . Int J Cardiol 2006;106:191– 195
Circulation. 2007;115:2103-2110
 Vasopressin and post CS vasodilatation

              Vasopressin deficiency?


•64 Consecutive Patients                 Control      NE      P
•Elected cardiac surgery                 (n=54)      (n=10)
•PCSVS treated with            LVEF% 55±10           45±15
                               <0.02
norepinephrine (NE)
                               Valve% 48              80      <103
•NE treated-patients
                               CABG% 39               0       <103
compared to others.
                               CPBt      123±46      220±87   <103




                 P Colson, Crit Care 2011; 15:R255
          Phe3
  Tyr2
                Gln4

                                       Vessels
Cys1
AsnS
  S5
         Cys6
 Pro7
   Arg8 Gly9NH
               2




                                         Flow




                                        MAP=SVR x CO

                       Venous return
 F redistribution
                                        Blood pressure
          Vasopressin in septic shock

779 patients
Post hoc substudy
75.6% corticoids
396 VP ; 382 norE

                      VP
VP+cort




           James A. Russell, for the VASST Investigators
                    Crit Care Med 2009; 37:811–818

				
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