Pharmacological and Clinical Aspects of Local Anaesthetics in the Elderly

1
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly

• Bernadette T. Veering, M.D., Ph.D.
• Dept. of Anesthesiology

LEIDEN UNIVERSITY MEDICAL CENTER, THE NETHERLANDS
2
(No Transcript)
3
Rembrandt
1606 - 1669
4
1890 2005
5
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly

• Introduction
• Age-related changes
• Clinical aspects
• Pharmacokinetic aspects
• Outcome regional vs general anaesthesia
• Conclusions and perspectives

6
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
7
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Age-related Changes in Anatomy

• decreased neuron density
• decreased number and diameter of myelinated
  fibers
• deterioration of myelin sheats
• increased permeability
• changes in the configuration of spinal
  curvatures
• sclerotic closure of intervertebral foramina

CNS
SPINE
8
Age-related Changes in Anatomy
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Spine
9
(No Transcript)
10
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Age-related Changes in Physiology

• slowing conduction velocity of peripheral nerves
  
• (motor nerves)
• decreased production CSF
• decline in baroreceptor reflex
• decline in thermoregulation

CNS
ANS
11

Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly

• Clinical Aspects

12
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly

• genito-urological procedures
• gynaecological procedures
• orthopaedic surgery
• hernia repair
• cataract surgery

13
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Advantages regional anaesthesia

• fewer thromboembolic complications

• reduced intra-operative blood loss

• decreased stress response to surgery

• preservation of pulmonary gas exchange

• better mental status immediately postop?

14
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Epidural Anaesthesia
Veering et al. Anesth Analg 19876589-94
15
Epidural Anaesthesia
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Ropivacaine
Levobupivacaine
Simon et al. Anesth Analg 2004 941325-30
Simon et al. Br J Anaesth 2004 93512-20
16
Thoracic Epidural Anaesthesia
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly

Hirabayashi and Shimizu. Br J Anaesth
199371445-6
17
Epidural Anaesthesia
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Parameter
Bupivacaine
Ropivacaine
Levobupivacaine
Analgesia
Time to max. caudad spread ? (?) (?) Time to
max. cranial spread (?) (?) Highest level of
analgesia ? ? ? 2-segment regression
? Time to total recovery
Motor blockade
Onset motor block ? Max. degree of
motor blockade ? ? Time to total
recovery
18
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Spinal Anaesthesia
Veering et al. Br J Anaesth 198860187-94
19
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Spinal Anaesthesia
Pitkänen et al. Br J Anaesth 198456279-84
20
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Effect of age on clinical profile Spinal
anaesthesia glucose-free solution
21
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Peripheral Nerve Blockade
Paqueron X et al. Anesthesiology 2002 921330-4
22
(No Transcript)
23

Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly

• Hypotension

24
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Sympathetic Nervous System
25
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Hypotension and spinal anaesthesia
Related to - height of analgesia ?
T5 - age ? 40 yr
Carpenter et al. Anesthesiology 199276906-16
26
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Hypotension and epidural anaesthesia

Simon et al. Anesth Analg 2002941325-30
27
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Spinal anaesthesia T4 SAP gt 33 SVR 26
Rooke et al. Anesth Analg 19978599-105
28
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Central neural blockade
sympathetic block

• prevention
• preloading i.v. fluids

• treatment
• vasopressor drugs with or
  without i.v. fluids

arterial vasodilatation venodilatation venous
return hypotension
29
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Haemodynamic effects of spinal anaesthesia
T6 SAP gt 25 SI SVRI HR CVP
colloid SVRI SAP
colloid ?-agonist SVRI SAP
Critchley et al. Br J Anaesth 199473464-70
30
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Preloading i.v. fluids

• crystalloids versus no prehydration
  no effect
• Coe et al. Anaesthesia 199045241-3

• crystalloids/colloids versus no prehydration
  no effect
• Buggy et al. Anesth Analg 199784106-10

31
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Veering et al. Br J Anaesth 200187738-42
Veering et al. Br J Anaesth 199677343-6
32
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Hypotension
Hip surgery Age 85 yrs Level T8-T9 Hyperbaric
bup SDSA 10-15 mg CSA 5-7.5 mg
Favarel-Garrigues et al. Anesth Analg
199682312-6
33
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Change in technique to avoid high level
Unilateral spinal anaesthesia Lateral position 15
min Inguinal hernia repair Age gt 60
yr Hyperbaric solution - 8 mg bupivacaine 0.5
- 8 mg levobupivacaine 0.5 - 12 mg ropivacaine
0.5
Unilateral spinal block T6 (operative side )vs
L3 (nonoperative side)
Casati et al. Anesth Analg 2004 991387-92
34
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
To avoid high level reduce dose local
anaesthetic
Hip surgery Aged gt 75 yrs Hyperbaric
solution 7.5 mg bup suf 5 µg vs 15 mg bup

decline in MAP bup suf lt bup
Olofsson C et al. Acta Anaesthesiol Scand 2004
481240-4
35

Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Conclusion Hypotension

• Incidence of hypotension - related to height of
  analgesia
• Preload with crystalloid or colloid - no
  prevention
• Colloid vasopressor ?-agonist - effective
  treatment
• first (5-10) min of spinal anaesthesia
• Avoiding a high level of analgesia - continuous
  spinal anaesthesia
• - unilateral spinal anaesthesia
• - reduced dose LA opioid

36

Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly

• Hypothermia

37
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Hypothermia
Vassilief et al. Anesthesiology 1995831162-6
38
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Hypothermia
Frank et al. Anesthesiology 2000921330-4
39
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Conclusion hypothermia in regional anaesthesia

• Incidence of hypothermia - related
  to height of analgesia
• - related to age
• Thermoregulatory thresholds? -
  high levels of analgesia

40

Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly

• Sensitivity to drugs

41
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Hyperbaric bup 15 mg 50 µg fentanyl O2
desaturation 25 µg fentanyl no
ventilatory effect
Varessi et al., Anaesthesia 199247558-62
Pre- and intraoperative benzodiazepines
Hyperbaric bup 12.5 mg 25 µg fentanyl O2
desaturation
Fernandez-Galinski et al., Anesth Analg
199683537-41
42
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Sedation
Shinozaki et al. Can J Anaesth 2002 49927-31
43
Pharmacokinetic
Aspects
44
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly

• FACTORS POSSIBLE EFFECTS
• increased body fat - greater volume of
  distribution of lipophilic local
  anaesthetics

• decline hepatic blood flow - decrease in
  clearance of local anaesthetics with
  high hepatic
  extraction ratio

• decline hepatic mass - decrease
  in clearance of (fewer functioning cells
  local anaesthetics with low hepatic
  extraction ratio)

45
Injection of Local Anaesthetic Agent
Spread near nerve structures
Vascular uptake in systemic circulation
Diffusion to neural tissues 'site of action'
SIDE EFFECTS
NEURAL BLOCKADE Clinical profile
46
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Pharmacokinetics of Local Anaesthetic Agents

• LOCAL DISPOSTION SYSTEMIC ABSORPTION
• diffusion to 'target'
• tissue binding 'fat'
• local vascular absorption
• SYSTEMIC DISPOSITION

47
Pharmacokinetics of Local Anaesthetic Agents
Effects of age
Veering et al. Anesth Analg 198766589-93
48
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Relation of Pharmacokinetics to
Pharmacodynamics
Pharmacokinetics Pharmacodynamics
(clinical profile)
Systemic absorption Duration of action
49
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
50
Systemic Absorption of Local Anaesthetics from
the Epidural and Subarachnoidal Space
Biphasic absorption pattern
initial phase
second phase
slow "uptake from fat"
epidural anaesthesia
rapid "vascularity epidural space"
spinal anaesthesia
slow "poor perfusion subarachnoid space"
slow
51
Systemic Absorption after Epidural and
Subarachnoid Administration
Effects of age

• Epidural anaesthesia
• Bupivacaine - no effect
• Ropivacaine - fraction during initial
  absorption phase ?
• Levobupivacaine - fraction during initial
  absorption phase ?
• faster initial absorption

• Spinal anaesthesia
• Bupivacaine - faster
  absorption

52
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Effects of age
Changes in the clinical profile

• not related to changes in the systemic absorption

• increased sensitivity probably related to
• - intrinsic neural sensitivity
• - altered local distribution

spinal
paraspinal
53
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Disposition clearance
Veering et al. Anesth Analg 198766589-94
54
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Disposition clearance
Simon et al. Anesth Analg 2005 102512-20
55
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Disposition clearance
Bowdle et al. Reg Anesth 198611123-7
56
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Pharmacokinetics Disposition

• clearances - bupivacaine, ropivacaine
  and lidocaine
  decrease with age

Infusion rates or top-up doses may need
to be adjusted
57

Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly

• Outcome
• Regional vs General Anaesthesia

58
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Postoperative Outcome

• mortality - short and long term

• cardiac - immediate and long term

• confusion - immediate and long term

59
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Outcome regional vs general hip operations
9.4 - 36.6 reg 8 - 32.6 gen
Suttcliffe et al. (Anaesthesia 199449237-40)
prospective
spin
1333
morbidity () Myocardial inf (7 days)
1.3 - 4.4 gen 1.6 - 5.4 reg
9425
spin/epi
2.0
O'Hara et al. (Anesthesiology 200092947-57)
retrospective
1.9
60
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Outcome regional general vs general Upper
abdominal surgery
gen reg 4.3 vs 5.1
Rigg et al (Lancet 2002 3591276-82)
epi gen vs gen
Myocardial infarction gen reg 13 vs 15
reg lt gen
915
- 72 hr epi cath
pulm. compl. reg lt gen 23.3 vs 30.2
61
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Incidence of cardiovascular diseases
62
Preoperative cardiac outcome

• Elderly patients (81 yr 8) at risk for CAD
  hip surgery

- preoperative epidural analgesia vs parenteral
analgesia (opioid LA) (i.m. opioid)
Matot et al. Anesthesiology 200398156-63
63
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Cardiac outcome regional vs general peripheral
vascular surgery
epi (T 8-10)
- 24 hr epi cath
gen reg 4.0 4.0
gen reg 2.0 2.0
Christopherson et al. (Anesthesiology
199379422-34)
100 gt 65 yr
- i.v. PCA (gen)
423 spin/epi i.v.
gen reg gen reg gt 68 yr
(T 8) morphine 7.3 6.7
2.7 1.5

Bode et al. (Anesthesiology 1996843-13)
64
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly

Perioperative Cardiac Outcome

• TEA gt LEA

Beattie et al. Anesth Analg 200193853-8
65
Cardiac outcome regional vs general
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly

• Hip fracture surgery gen
  reg
• incidence DVT ?

• Upper abdominal surgery gen reg

• Peripheral vascular surgery gen reg

• Epidural p.o. analgesia
  reglt gen TEA ?LEA

66
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Immediately postoperative confusion
Predisposing factors

• preoperative medication - anticholinergics
• - neuroleptics

• preoperative signs of loss of memory

• dementia

• depression

• ASA-status

• type of operation

67
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Postoperative cognitive dysfunction

• Regional versus general anaesthesia

• 1 week reg lt gen
• 3 months gen reg

Rasmussen LS et al.
Acta Anaesthesiol Scand 200347260-6

• Age increased the risk of late post-operative
  cognitive dysfunction
• Moller et al. Lancer 1998 351857-62

68
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Conclusion Postoperative Cognitive Dysfunction

• Regional anaesthesia may decrease the incidence
  of POCD early after surgery

• Physical and mental condition are important

• Increasing age and type of operation

69

Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly

• Conclusion and Perspectives

70
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Increased sensitivity to local anaesthetic agents

• Clinical profile
• block height ? consequence
• duration of block ? smaller doses

Pharmacokinetics clearance ?
consequence continuous blockade infuse rate
? top up dose ?
71
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Conclusion

• Technical difficult chance of
  failure

• Sensitivity? dose requirement? ?
• -local anaesthetics
• -opioids
• -benzodiazepines
• -propofol

72
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Conclusion

• Hypotension main side-effect
• ? level of analgesia - SVR
  
  - effective
  treatment colloid
  vasopressor first (5-10) min of spinal anaesth

• Hypothermia older patients at risk
• ? level of analgesia
• - carefully monitoring body
  temperature

73
Pharmacological and Clinical Aspects of Local
Anaesthetics in the Elderly
Perspectives

• Future studies - combined pharmacokinetic -
  clinical
• profile studies

- characterisation of local disposition
- to design optimal dose
regimen - single injection - continuous
administration
74
Combined Pharmacokinetic Clinical Profile Study
NONMEM population kinetics
Duration of analgesia at each dermatome
Absorption
PK/PD-model
Covariates
- Local anesthetic agent - Age - Weight - Height
Data derived from (n91) Burm et al., 1987
Bupivacaine 0.5 (n6) Veering et al., 1992
Bupivacaine 0.5 (n19) Simon et al., 2004
Levobupivacaine 0.5 (n15) Simon et al., 2004
Levobupivacaine 0.75 (n27) Simon et al., 2005
Ropivavacaine 1.0 (n24)
75
(No Transcript)