?atast???, ??a???s?a, ??????as? se ?ef???? ?a? ?pat??? d?s?e?t?????a

1
?atast???, ??a???s?a, ??????as?se ?ef???? ?a?
?pat??? d?s?e?t?????a

• ?as???? ?. ??d?a?????
• ??a?s??s??????? - ??tat????????
• ?p?µe??t?? A ???/??T ???

2
(No Transcript)
3

• 68 as?e??? ?aµß????? ?atast??? ?at? t? d????e?a
  t?? ???
• ? ???s? t?? ?atast???? s??d????e µe pa??tas? t??
  ???, pa?atetaµ??? weaning ?a? µe?a??te?? ?????
  pa?aµ???? st? ??T
• 13 t?? as?e??? ??aße µ?????as?
• ?? as?e?e?? p?? p??a? µ?????as? e??a?
  pa?atetaµ??? ???, weaning, ????? pa?aµ???? st?
  ??T ?a? µe?a??te?? ???t?t?ta.

4
??? µe???e? ?at?????e? fa?µ???? p??
???s?µ?p?????ta? st? ??T Sedative-hypnotic
agents ?a? Opioid analgesics, ??asfa??????
a?????s?, ?atast???, aµ??s?a ?a? a?a???s?a st??
as?e??
5
?atast??? propofol (40)?a? midazolam
(34) ??a???s?a fentanyl (36) ?a? morphine
(22).
6
(No Transcript)
7
Effects of Anesthetic Drugs on Renal Function

• Decreases in RBF, GFR, urine output
• Nephrotoxicity (Fluoride ion-polyuria)

8
Pk Parameter Healthy individual Critically ill patient variation Increases Decreases Critically ill patient variation Increases Decreases
Vd One compartment model Two compartment model Volume resuscitation Ascites Capillary leak Edema Dehydration Volume loss Diarrhea/Vomitting
Pb Total protein 5-7 Albumin 3-5 IVIG administration Albumin administration Adequate nutrition Hypoproteinemia Hypoalbuminemia Acidosis / Fever / Uremia Medication competition
Cl First order kinetics Zero order kinetics Hemodialysis Peritoneal dialysis CRRT Oliguric renal failure Anuric renal failure Shock states
t1/2 First order kinetics Zero order kinetics Oliguric renal failure Anuric renal failure Shock states Hemodialysis Peritoneal dialysis CRRT
9
CRRT ep?d?as? st? fa?µa??????t???

• Usual circuit priming volume 100-150mL
• Increases Volume of Distribution (Vd)
• Usual adult blood volume 5000mL
  (0.07L/kg or 70mL/kg)
• Usual pediatric blood volume 80mL/kg
• Tubing binds drug
• Increases Vd
• Adsorption
• Membrane Filter binds drug by Gibbs-Donnan
  Effect
• Increases Vd
• Adsorption

10
CRRT Impact on Kinetic Parameters

• Usual Blood Flow Rate 3-5mL/kg/min
• Higher the rate leads to increased Clearance (Cl)
• Ultrafiltrate Rate Filter Replacement Fluid
  (FRF) Rate if the patient is kept in even fluid
  balance 35-40mL/kg/hr (2.5L/m2/hr)
• Higher the rate leads to increased Cl
• Dialysate Rate 35-40mL/kg/hr (2.5L/m2/hr)
• Higher the rate leads to increased Cl

11
???? a???s?? t?? e???ef????? ???a?s?? ?at? t?
CRRT t?t??p???s? t?? d?se?? fa?µ???? ?at?st???
(Midazolam, Lorazepam, Fentanyl,
Morphine) ???e??s?spast??? (Norepinephrine,
Epinephrine, Dopamine) ???t??pa (Milrinone,
Dobutamine, Epinephrine)
12
??a???s?a

• ??s?? pa?eµß?se??
• S??a?s??µat??? d?ata?a?? ?????
• Goals a?????s? , ap??e?a s??e?d?s?? , s??e??as?a
  , aµ??s?a ?a? a????s?a

13

• ??a f??µa?? p?? ?p?ß???eta? se ??????? ?a? p????
  µetaß???sµ?, a?e???t?t?? t?? d????e?a? ????s?? ?
  a?ep???e?a? ???????

14
Commonly used Opioids
RELATIVE POTENCY T ½ (Hr) ACTIVE METABOLITES
MORPHINE 1 2.2 MORPHINE-6- GLUCURONIDE
MEPERIDINE 0.1 3.2 NORMEPERIDINE T1/2 15 HRS
FENTANYL 100 4 NONE
HYDROMORPHONE 7 NONE
SUFENTANIL 500 2.7 NONE
REMIFENTANIL N/A NONE
ALFENTANIL 10 1.2 NONE
METHADONE 1 19 NONE
15
Fentanyl, alfentanil and sufentanil

• S???et??? ?p??e?d?
• ?p??e??ta? se ?pat??? µetaß???sµ?
• ? s??e??? ????s? ?d??e? se s?s??e?s? ?a? pa??tas?
  t?? fa?µa?e?t???? d??s??

The place for short-acting opioids special
emphasis on remifentanil Wolfram Wilhelm1 and
Sascha Kreuer2 Critical Care 2008, 12(Suppl 3)S5
(doi10.1186/cc6152)
16
(No Transcript)
17
Remifentanil pharmacology

• µ-opioid receptor agonist
• terminal half-life 10 to 20 minutes
• context-sensitive half-time is 3 to 4 minutes
• Completely metabolized by unspecific esterases
• Remifentanil acid (RA)

18
Evans and Park reported successful use of
remifentanil for analgesia and sedation during
mechanical ventilation for 3 to 33 days. The
infusion rate ranged from 0.08 to 0.43 µg/kg per
minute (modal values), and all patients exhibited
signs of recovery within 10 minutes of stopping
the remifentanil infusion.
Evans TN, Park GR Remifentanil in the critically
ill. Anaesthesia 1997, 52800-801.
19
One of the most important issues in
neuroanesthesia and neurocritical care is
neurologic assessment. Therefore, cessation of
analgesic and sedative infusions should
be accompanied by rapid and predictable
awakening, thus allowing clear differentiation
between brain dysfunction and over-sedation.
Karabinis A et all Safety and efficacy of
analgesiabased sedation using remifentanil versus
standard hypnoticbased regimens in intensive care
unit patients with brain injuries a randomised,
controlled trial ISRCTN50308308. Crit Care
2004, 8R268-R280
Bauer C, et all Remifentanil-propofol versus
fentanyl-midazolam combinations for intracranial
surgery Influence of anaesthesia technique and
intensive sedation on ventilation times and
duration of stay in the ICU. Anaesthesist 2007,
56128-132.
20
SedationBenzodiazepines
T ½ Hr Protein Binding Active metab. Metabolism
Diazepam 46.6 97.8 Desmethyl diazepam (t1/2 48-96 hrs) Liver
Midazolam 3.0 94 None Liver
Lorazepam 14.5 91 None Glucuronyl transferase
21
? pa??tas? t?? d??s?? t?? ??da????µ?? µp??e? ?a
ap?d??e? st? s?ss??e?s?, st?? ?pat???
a?ep???e?a, ? se ??a e?e??? µetaß???t?, t??
a- hydroxymidazolam, p?? ap?ß???eta? ap? t???
?ef???? ?a? µp??e? ?a ?d???se? se pa??tas? t??
?atast???? st??? as?e?e?? µe ?ef???? a?ep???e?a
Patient-Focused Sedation and Analgesia in the ICU
Curtis N. Sessler and Kimberly Varney Chest
2008133552-565
22
SedationBarbiturates
Types Names T 1/2
Long acting Phenobarbital 24-96 hrs
Medium acting Pentobarbital Secobarbital 20-45 hrs
Ultra short acting Thiopental Methohexital 4-24 hours
23
???p?f???

• ?atasta?t???, a?a?s??t???, aµ??s?a??,
  spasµ???t???
• ??ap?e?st??? ?a? CV ?atast???
• ????? d?a??t?t?ta st? ??p??
• G?????? ??a??? µ???? d????e?a
• Onset lt1 min, peak 2 min, duration 4-8 min
• ? ???a?s? de epe??e??eta? se ?ef???? ?a? ?pat???
  a?ep???e?a

24
NMB

• Large highly charged water-soluble molecules at
  physiologic pH ?cant cross BBB, placenta, GI
• Onset is more rapid less intense at the
  laryngeal ms (vocal cord) peripheral ms
• Diaphragm is the most resistant to paralysis
• Type
• Depolarizing mimic action of Acetylcholine
• Non-depolarizing competitively block ACH
  receptors
• Classifications
• Short Succinylcholine, mivacurium
• Intermediate Atracurium, Vecuronium, Rocuronium,
  Cisatracurium
• Long Pancuronium, Doxacurium, Pipecuronium

25
Metab./ excretion Onset (min) Duration (min) Dosage (mg/kg) Infusion
Succinylcholine Pseudo-cholinest. 1 3-4 IV- 1-2 IM-3-4
Mivacurium Plasma Cholinester 1-3 9-12 0.2 10-14 mcg/kg/min
Atracurium Hoffmann 1-4 20-35 0.3-0.4 0.6-1.2 mg/kg/hr
Cisatracurium Hoffmann 2-3 35-45 0.1-0.2 0.06-0.24 mg/kg/hr
Vecuronium Liver Renal exc. 1-3 30-40 0.1 0.06-0.15 mg/kg/hr
Rocuronium Liver Renal exc. 1 30-90 0.5-1 10-20 mcg/kg/min
Pancuronium Liver Renal exc. 2-3 40-60 0.1 0.02-0.1 mg/kg/hr
Pipecuronium Liver Renal exc.
Doxacurium Renal 5-11 30 0.03-0.05 6-12 mcg/kg/hr
26
???a??st?