Transcript Anesthetic Choice/Management

Long Term Consequences
Perioperative management implications for
cancer patients
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1980’s Anesth mortality was 1:10,000 now
this is closer to 1:100,000
Δ Mandated SpO2, ETCO2, NIBP,ECG and AAM technology
10% all cause mortality (age 65+) in the year after surgery
is 10,000 X more common than preventable anesthetic
deaths but ......
Increasing evidence suggests PeriOp management may
have long term consequences –
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90’s periOp B blockers reduce all cause
mortality @ 1 year ( Swedish study with
Atenolol)
NA studies had more aggressive end pts and
there was a significant increase in PeriOp
strokes
Spinals/epidurals (pelvic,urologic,major
ortho) blood loss , DVTs, chronic incisional
pain and PONCD
Terri Monk – BIS monitor observational study
reported a 3 fold increase in one year mortality
in elderly patients with deep anesthesia. This has
now spawned the “B Aware” trials. She also
noted;
 More pronounced effects of anesthetic agents in
patients with carcinoma and commented on;
 Significant adverse long term consequence to
GA esp at the extremes of age
 Learning & behavioural issues ≤ 2 years (possibly
age three in most recent studies)
 Neurocognitive decline - elderly
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“We must investigate the mechanisms by
which patients with cancer respond to
standard anesthetic doses with more
pronounced cortical electrical depression and
how pharmacokinectics and dynamics are
altered in pre existing disease states”
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IARS Smart Tots® research initiatives on
pediatric inhalational anesthesia (neuroplasicity, agent toxicity vs stress) i.e.
This is more than separation anxiety!
Ketamine ( nmda receptor inhibitors)
Illicit substances ( Ecstasy, Amphetamines,
Cocaine, crystal meth ......)
Etomidate
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Surgical manipulation – tumor cell release
into lymphatics and blood stream
Micro metastases already present prior to
surgery
This MINIMAL RESIDUAL DISEASE can result
in clinical mets when there is a balance shift
between the patient’s immune status and the
tumors’ ability to seed,proliferate and attract
new blood vessels
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Tumor cells released into circulation
cell mediated immunity ( T cell and NK cell
function)
Increased Vascular Endothelial and other
growth factors ( Normally promote wound
healing but are pre empted by malignant
cells)
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Dose/patient specific dependent depression
of neutrophil, macrophage, dendritic cell, T
cell and NK cell immune functions
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Morphine, and to a lesser degree synthetic
narcotics, decrease cellular and humoral
immune function. Systemic administration
has been associated with a proangiogenic
action promoting tumor growth.
By contrast most non opiod analgesia
preserves NK cell function and, in rodents,
reduces metastatic tumor spread.
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Red – single nucleotide
polymorphisms
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MOR – u opiod receptor
VEGF – vasc endo growth
factor
Various mammallian tumor
cell lines result in enhanced
specificity of the mediators
of angiogenisis
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Genotype stratification was correlated to
breast cancer specific mortality
One further observation re European
American vs Afro American breast cancer
survival data
Prevent Neuroendocrine Stress by;
1. Blocking afferent neural traffic
2. Blocking descending efferent activation of
the sympathetic nervous system
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Note: narcotic doses required to generate a
stress free surgical anesthetic are
impractical in most instances.
 If pre incision functioning block then 
Neuroendocrine stress
  volatile anesthetic requirements
  post op opiods
  endogenous opiods (endorphins)
Caveat: adequate perfusion pressure
 Paravertable blocks; 4 fold  in recurrence or
mets in breast Ca
 Primary melanoma excision; if GA vs local or
regional anesthesia: -ve predictive value 1.46
for survival
 Epidural anesthesia for Radical
Prostatectomy, colonic cancer surgery and
Ovarian Serous Adenocarcinoma – variable
but  survival or “cancer free” period
 Blood transfusion
 Glucose control
 Fluid management
 Inhalational anesthetic toxicity – newborns
 Persistent incisional pain
 Beta blockers
ᾄ agonists – clonidine
 NSAIDS
 NMDA receptor blockers
 central
 A subset of the CSP #345 ; the effect of Epidural
Anesthesia/analgesia on perioperative outcome
 Prospective, randomized
 Aortic,gastric,biliary and colonic surgery Mar 92 to
August 94 – followup to Dec 2002
 Epidural .5% bupivacaine, Epi 1:200,000 : T6 block
prior to GA
 End pts; ,MI,CHF,HB,BP,PE,Resp failure,cerebral
insults,ARF : were all NS at 30 days
 Post op pain, ambulation, LOS
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247 pts with complete followup of 177
also of note: 70 not in study had similar
survival experience
92 GA, 85 EGA
IV post op opiods or 48+ hours epidural
analgesia
GA: Isoforane, N2O,Vecuronium,fentanyl
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N=42151 with 23% epidural during resection
1996-2005, > 65 years with 4 year follow up
minimum
> 1 year increase all cause survival in epidural
group
No change in cancer reccurance rate
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Patients for RP Jan 94- Dec 03 f/u to Oct 06
GA; fentanyl 1-2 ug/kg, propofol 12mg/kg,.5mg/kg atracurium N2O/O2,
Diclofenac 75-100 bid
T11-12 epidural Rx prior to surgery vs post op
IV PCA
If Epidural patients required post op IV
morphine they were included in the GA
group n=6
GA/PCA =123, Epidural/GA =102 : #s in each
group determined by preferences, relative
contraindications etc
  was NS but ASA score,complications &
surg time in epidural group
 Primary outcome “biochemical recurrence” ie
 PSA from post op nadir  possible Rad Rx,
endocrine or chemo Rx
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retrospective study
Jan94-June97 n=103 GA+TEA, 45 not incl re
inadequate TEA
 July97-Dec2000 n=158 GA+
Morphine/Ketoloric
 Primary Outcomes
 Biochemical recurrence free survival
 Clinical progression free survival
 Cancer specific survival
 Over all survival
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Standardized GA incl fentanyl 2 ug/kg,
N2O,forane
T10-12 TEA .25% bupivacaine 8-10 cc/hr, No
COX inhib
PostOp .1% bupivacaine/fentanyl 2ug/cc @ 815 cc/hr X 48 hrs
Limitations TEA group – higher ASA, 2X
infusion rate and less fentanyl (confounding
variables)
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Excess prostaglandin release and
endogenous cortisol  immunosuppression
NSAIDS inhibit prostaglandin synthesis
Cyclooxyngenase 2 is induced in “tumor
promoters” – prostaglandin synthesis
increase prostate cell lines while COX2
inhibitors induce apoptosis (cell death)
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327 mastectomy/Axillary dissection chart
reviews – 1 surgeon, 1 Oncologist, 2
anesthetists ( Feb ‘03- Sept ‘08)
8 excluded re pulm mets, incomplete op etc.
Pre incision: Clonidine or Ketamine or
Ketoloric, all received postOp diclofenac &
acetaminophen
GA sufentanil, STP or propofol, Sevo or Des
plus Air/Oxygen
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Retrospective review Aug 1999 – Dec 2009 ;
179 consecutive pts with < 3cm hepatic
tumors
End points - overall and recurrence free
survival
Epidural (T8-10 1.5% lidocaine) vs GA
(Fentanyl, Propofol TIVA)
Study limitation – adequate epidural
anesthesia was not defined
Study results ???
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Recurrance free survival; Epi vs GA (3.66), Tumor
# (2.28), GGT ( 1.39)
 Overall survival; Liver function (2.30), Tumor #
(2.36) GA no benefit in overall survival
 Inverse probability weighted Epi vs GA = 1.26
Epidural anesthesia for this procedure can be
associated with referred pain requiring add’n
opiods. This could also limit current intensity or
duration of therapy. Epi patients did not have
any opiod sparing in the post op period.
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Mortality during a 10 yr Obs study
52 SpA vs 221 GA
Trend toward better Cumulative survival rates
in patients who received spinal anesthesia:
SpA 96 months (CI 81-111)
GA 69 months (CI 50-88)
What do we know about surgical stress response and
Cancer?
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Opiods – analogs of
morphine – u3
Cox inhibiters
Alpha adrenergic
antagonists
Beta blockers
Inhalational
anesthetics
Regional anesthesia
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TRIM ( transfusion
related
immunomodulation)
Hypothermia
Sepsis
Statins
Etomidate
The answer is : IT DEPENDENDS
Malignant tumors
invade extracellular
matrix
 Surgical clamping
triggers a reperfusion
injury by upregulation
of MMP9
(neutrophils,a rich
source of MMP9,
accumulate because of
IL 8)
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Complex in vitro study
demonstrated volatile
anesthetics reduce
reperfusion injury – this
is not new
 But indices of
colorectal matrix
invasion were reduced
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Data suggests;the possibility that anesthetic
conduct may contribute to the recurrence of
cancer ( liberal opiod Rx or inadequate
analgesia)
Equally worrying is the possibility that
anesthesia, or the stress response to surgery
could activate dormant cancer cells in an
individual undergoing non cancer surgery.