2. Hypothermia
Used first for TBI by Fay in 1945
Bigelow performed experiments in 50`s
I`st ASD closure in 1952 by dr john lewis under
hypothermia
After the first years of enthusiasm, however,
deep hypothermia was vastly abandoned in
noncardiac surgery
During the subsequent 30 years as a result of
thefrequent occurrence of severe complications
such as systemic infections, fluid and electrolyte
imbalances and cardiovascular instability
Resurgence in use since 80`s with mild
3. Basis for usage
Rate of biologic reactions changes linearly with
temperature
Rate of biologic reactions(due to enzymatic
involvement) however decreases exponentially
with temperature
Q10 : factor by which rate changes over a
temperature change of 10 °C
For most biologic reactions value of Q10 is in
range of 2-3(310k-300k)
5. In humans CMRO2 decreses 5-7%/°C fall in
temperature
This low metabolic rate maintains the demand
and supply ratio even at low blood flows due to
low requirement
In other words hypothermia increases the
tolerance of cells towards ischemia
Window period before ischemic injury occurs is
directly related to degree of hypothermia
6.
7. Degrees of hypothermia
Mild : 32-34 °C
Moderate : 25-32 °C
Deep : 14-25 °C
Electrical silence : 12-18 °C
8. possible sites of action
Decreased excitotoxicity
Decreased necrosis and apoptosis
Decreased microglial cell activation
Oxidative stress modulation
Decreased inflammation post ischemia
9. Excitotoxicity
Ischemia:ATP depletion which leads to
loss of ion gradients and accumulation
of intracellular K+ and Na+
Glutamate release and decreased
uptake
Excessive Ca+ influx and cellular
hyperexcitability
10.
11.
12.
13. Late consequences
Cytotoxic edema
Vasogenic edema
Dysfunctional BBB : increased interstitial water
movement and rise of pericellular hydrostatic
pressure
14. Necrosis and apoptosis
Hypothermia decreases cytochrome c release
Decrease caspase activation,DNA fragmentation
15. Decreased microglial activation
Less production of IL-6 and NO
Inhibition of glutamate induced NO synthesis
Supression of neutrophil accumulation
16. Acid base balance
pH: 7.40 & pCO2: 40 mm of Hg at 37 deg C.
The solubility of gases increases with fall in
temperature
The change in [H+] and pH that occurs with
change in temperature is independent of a
change in CO2 content, and therefore does not
depend on the change in CO2 solubility with the
temperature change
17. All acids and bases, including water, exist in
solution in equilibrium between the undissociated
form and the ionized components of the parent
molecule. The dissociation constant (K) is the
equilibrium ratio of the product of the
concentrations of the ionized components to the
unionized component. For water at 25°C, the
equilibrium dissociation equation is as follows:
18. pH and pN
pH= - log [H+] i.e ; - log 1* 10-7 = 7
Dissociation is directly proportional to
temperature
In temperature range seen in clinical CPB
(approximately 15°C to 40°C), the dissociation
constant of water increases from 0.451 × 10-14 to
2.919 × 10-14
Change in [H+] from approximately 67 nmol/L at
15°C to 170 nmol/L at 40°C
19. Water(universal solvent)
Hence water changes from weak base to weak
acid with increase in temperature
The major importance of this concept is that
water is the fundamental solvent of all biologic
systems and the dissociation of virtually all weak
acids and bases in biologic solutions follows the
same pattern as that described for water
20. Blood buffers
At normal body temperature (37°C), blood and
tissue fluids are alkaline relative to water at the
same temperature
A number of buffer systems create and maintain
this relative alkalinity so that the ratio of [OH-] to
[H+] remains constant at approximately 16:1
despite temperature variation
As temperature changes, the intrinsic dissociation
of these buffer systems also changes to maintain
the ratio of [OH-] to [H+] constant
21. Importance of histidine
A major buffering system responsible for this is
the imidazole moiety of the amino acid histidine,
which is commonly found in body proteins.
The pKa of histidine is close to 7.0 at body
temperature
confers potent buffering capacity for maintaining a
constant ratio of [H+] to [OH-] despite significant
changes in the absolute concentration of each as
temperature varies
23. What is alpha?
The ratio of the unprotonated histidine imidazole
groups to H+, a value known as alpha, remains
constant
Total CO2 also remains constant
pH changes as per the changes in temperature
Reaction kinetics of numerous respiratory
enzyme systems show optimal catalytic function
with temperature change when the pH of the
reaction medium parallels the temperature
mediated pNH2O change
This method is hence known as alpha stat
strategy
24. pH stat
Alternative method of acid-base strategy is pH-stat. With
this method, pH is the value that is maintained constant at
varying temperatures.
Hibernating mammals maintain a pH-stat strategy
These animals hypoventilate as they hibernate, the tissue
CO2 stores increase, and intracellular pH becomes acidotic
in most tissues.
This acidotic state causes a further depression of
metabolism that may be useful by further decreasing the
energy consumption of nonfunctioning tissues, such as
skeletal muscle, gastrointestinal tract, and higher brain
centers.
In contrast, active tissues, such as heart and liver, adopt a
different strategy by actively extruding H+ across their cell
membranes to maintain intracellular pH at or near the
values predicted by the α-stat methodology.
Therefore, hibernating mammals are able to vary their
intracellular-to-extracellular pH gradient differently in
different tissues, depending on the state of metabolic
25. Organ function
Hypothermia causes a decrease in blood flow to
all organs of the body
Skeletal muscle and the extremities have the
greatest reduction in flow, followed by the
kidneys, splanchnic bed, heart, and brain.
Despite this decrease in flow, differences in the
arteriovenous oxygen content are seen to either
decrease or remain unchanged, which implies
that the oxygen supply is adequate to meet the
metabolic requirements
26. Heart
With cooling, heart rate decreases but contractility
remains stable or may actually increase
Dysrhythmias become more frequent as temperature
decreases and may include nodal, premature
ventricular beats, atrioventricular block, atrial and
ventricular fibrillation, and asystole
The mechanism of this dysrhythmogenic effect is
unknown but may involve electrolyte
disturbances, uneven cooling, and autonomic nervous
system imbalance.
coronary blood flow is well preserved during
hypothermia, it is unlikely that myocardial hypoxia
plays a role in the genesis of these dysrhythmias
27. Pulmonary system
The pulmonary system is characterized by a
progressive decrease in ventilation as the
temperature is lowered
Physiologic and anatomic dead space increases
during dilation of the bronchi by cold.
Gas exchange is largely unaffected
28. Renal function
The kidneys show the largest proportional decrease in
blood flow of all the organs.
Hypothermia increases renal vascular resistance, with
diminished outer and innercortex blood flow and
oxygen delivery.
Tubular transport of sodium, water, and chloride are
decreased.
Urine flow may be increased with hypothermia, but
this effect can be masked by the stress-induced
release of arginine vasopressin
The ability of the hypothermic kidney to handle
glucose is impaired, and glucose often appears in the
urine
Hemodilution in combination with hypothermic CPB
improves renal blood flow and protects the integrity of
29. Metabolic changes
Hepatic arterial blood flow is reduced
Decrease in metabolic and excretory function of
the liver
Marked hyperglycemia due to decreased
endogenous insulin production,glycogenolysis
and gluconeogenesis because of increases in
catecholamines
Even if exogenous insulin is administered, its
efficacy is reduced during hypothermia
30. Vascular system
Tissue water content is increased due to hemodilution.
Cell swelling and edema occur, which may be related to an
accumulation of sodium and chloride within cells secondary to a
decrease in reaction rates of membrane Na+ -K+ -ATPase
SVR and PVR typically rise with cooling below 26°C
Arteriovenous shunts appear at low temperatures and may
cause a further diminution in tissue oxygen delivery
The increase in blood viscosity occurs because of fluid
shifts, with loss of plasma volume from capillary leak and cell
swelling
The red blood cell volume remains unchanged although the
hematocrit rises. Red blood cell aggregation and rouleaux
formation can occur, further impeding blood flow
These changes can be attenuated by adequate
anesthesia, hemodilution, heparinization, and the use of
vasodilators.
Thrombocytopenia by a reversible sequestration of platelets in
the portal circulation
31. DHCA
The most dramatic application demonstrating the
protective effects of hypothermia is in DHCA.
Systemic temperatures of 20°C to 22°C or less are
used to allow cessation of the circulation
In pediatric cardiac surgical patients (particularly
those weighing < 8 to 10 kg) the repair of complex
congenital cardiac lesions is often facilitated by the
asanguineous surgical field provided with circulatory
arrest
It is often used in procedures requiring occlusion of
multiple cerebral vessels, particularly repair of aortic
arch aneurysms.
It may be used to enhance surgical exposure and
speed in procedures that could lead to uncontrollable
hemorrhage
32.
33. Organ protection during DHCA
Hypothermia
Pharmacological adjuncts
Perfusion strategies
Topical external cooling of the head
optimized acid-base management
pump prime modifications
leukocyte depletion
The degree of hemodilution
strategies of cooling and rewarming
34. Conduct of DHCA(temperature)
The cooling phase should be gradual and long
enough(20-30 mins) to achieve homogenous
allocation of blood to various organs and to
prevent a gradual updrift of temperature during
DHCA
Rapid cooling might create imbalance between
oxygen delivery and demand by increasing the
affinity of hemoglobin to oxygen.
This increased affinity combined with extreme
hemodilution from the priming solution for CPB
might lead to cellular acidosis before DHCA
35. Degree of hypothermia required
Approximately 60% of the brain’s energy
consumption is used to transmit nerve impulses;
the remaining 40% is used for preservation of
cellular activity.
Electrocerebral silence occurs at about 17°C
nasopharygeal temperature
Although animal evidence suggests better
neuroprotection at temperatures of 8-13 °C
High degree of choreathetosis was seen in
humans subjected to these temperatures post.op
Hence general practice is to cool to 15-20 °C
before instituting circulatory arrest
36. Oxgen dissociation curve
Theoretically,
hypocarbia (and
increased pH)
result in a
leftward shift of
the
oxyhemoglobin
dissociation
curve, which
causes oxygen to
be less readily
available to the
tissues
However, more
oxygen is
dissolved in the
plasma during
hypothermia, so
that these two
effects tend to
cancel out each
other
37. Topical cooling
Delay in temperature equilibrium may occur
because of occlusive vascular disease that
reduces cerebral perfusion
Icepacking of the skull enhances cerebral
hypothermia via conduction across the skull
Helps to keep body temperature around 10° to
13°C
Prevents undesirable rewarming of the brain
Systems of continuous cooling of the head during
DHCA recently have been developed
Consist of a cooling cap with an incorporated
circuit of continuously circulated water at a
38. Boston trial
Boston Circulatory Arrest Trial prospectively
observed the neurological outcome of 171
neonates with Dtransposition of the great arteries
that were randomized either to DHCA or to low-
flow CPB for the arterial switch operation
In immediate post op period incidence of seizures
was higher in DHCA group
One year after surgery risk of delayed motor
development was more in DHCA group
These risks were proportional to amount of time
spent in DHCA
40. Rewarming
Rewarming increases CBF and the risk of embolization,cerebral edema,
and hyperthermic brain injury
During rewarming extracranial sites of temperature monitoring
underestimate brain temperature by about 5° to 7°C
May result in brain hyperthermia during rewarming
Perfusate temperature should not exceed core body temperature by
more than 10°C; to stop rewarming when core body temperature is
36°C (esophageal) or 34°C (urinary bladder) and for perfusate
temperature not to exceed 36°C
Relative hypothermia (36°C, esophageal; 34°C, urinary bladder) might
be beneficial
If EEG shows electrical hyperactivity decrease in temp./deepening of
anaesthesia should be instituted
Initial reperfusion with relatively cold blood at low pressures allows
washout of accumulated metabolites and free radicals and provides
substrates for high-energy molecules.
A period of initial hypothermic perfusion has been shown to improve
neurologic outcome
41. Cerebral blood flow decreases with hypothermia
esp. with alpha stat management
Autoregulation may be impaired at moderate to
deep hypothermia
CBFV is not detectable below CPP of 9mm of Hg
induced by low flow state
A minimum CPP of at least 13 mm of Hg was
required to attain a measurable CBFV
43. Alpha or ph stat
Acid-base management may be critical in the setting of
deep hypothermia.
Proponents of the α-stat method suggest that pH-stat
management may put the brain at risk for damage from
microemboli, cerebral edema, or high intracranial
pressure, or may actually predispose to an adverse
redistribution of blood flow (“steal”) away from marginally
perfused areas in patients with cerebrovascular disease.
On the other hand, proponents of the pH-stat strategy
suggest that enhanced CBF may be helpful in improving
cerebral cooling before the initiation of circulatory arrest.
In fact, total CBF is increased, global cerebral cooling is
enhanced, and brain blood flow is redistributed during
pH-stat management.
44. Alpha or ph stat
An increased proportion of CBF is distributed to deep
brain structures (thalamus, brainstem, and
cerebellum) with ph stat
However, other data suggest that cerebral metabolic
recovery after circulatory arrest may be better with the
α-stat method than with the pH-stat mode
This variation in results has led some authors to
advocate a crossover strategy in which a pH-stat
approach is used during the first 10 minutes of cooling
to provide maximal cerebral metabolic suppression,
followed by an α-stat strategy to remove the severe
acidosis that accumulates during profound
hypothermia during pH-stat.
This approach appears to offer maximal metabolic
recovery in animals
45. Alpha or ph stat
α-stat management will result in lower cerebral
flows than those seen with pH-stat management
However, because of the lowered metabolic
demands, a lower CBF may be appropriate and
indicative of a maintained coupling of blood flow
and metabolic demand
Coupling of CBF and metabolism that was
independent of cerebral perfusion pressure (CPP)
within the range of 20 to 100 mm Hg when α-stat
management was employed
Cerebral autoregulation was abolished and CBF
varied with perfusion pressure when pH-stat
strategy was used
47. When to use alpha stat ?
Throughout hypothermia in adult patients
generally in which luxury flow will increase the
embolic load
During rewarming in pediatric patients as it
provides better cerebral metabolic recovery
CBF decreases linearly with the decrease in
temperature, whereas CMRO2 drops
exponentially.The net result is that CBF becomes
more luxuriant at deep hypothermic
temperatures.
• At normothermia, the mean ratio of CBF to
CMRO2 is 20:1, and at deep hypothermia, the
ratio increases to 75:1
48. When to use pH stat then?
In pediatric patients with aortopulmonary
collaterals cerebral cooling can problematic
It appears that the addition of CO2 during cooling
enhances cerebral perfusion and improves
cerebral metabolic recovery in this group
An increase in pulmonary vascular resistance and
a decrease in pulmonary blood flow with the pH-
stat strategy also helps
Also to provide homogenous cooling while
instituting hypothermia
53. Degree of hemodilution
In past hematocrits in range of 10-30 have been
used
Hemodilution is not only a problem for red cell-
dependent gas transport, but also for platelet and
humoral factor-dependent coagulation and
protein dependent intravascular oncotic pressure
Recent data suggests maintaining hct in range of
25-30 provides better outcomes
Higher hematocrits improve tissue flow and
metabolism and decrease leukocyte and
endothelial cell activation
54. Monitoring
Standard ASA monitoring
Arterial catheter
Pulmonary artrey cath if indicated
TEE
Jugular bulb oximetery and temperature
NIRS
Trans cranial doppler
EEG,BIS
SSEP
55. TEE
Cardiac function before and after DHCA
Examination of aorta
Confirming canula placement
Assesing volume status
Determining adequeacy of repair
Detecting intra cardiac air
56. Temperature
As 99% of jugular blood flow originates from brain
circulation it is regarded as gold standard
During cooling phase nasopharyngeal
temperature corresponds to jugular temp.
During rewarming all sites lag behind
Caution has to be exercised to avoid hypothermic
insult
57. Jugular oximetery
Oximeter catheters transmitting three
wavelengths of light are used
Directly and continuously measure cerebral
venous oxygen saturation
recent study observed a much wider 45% to 70%
range in healthy subjects.
Furthermore, the 95% confidence interval of the
low threshold was 37% to 53%
58. Limitations
Sjvo2 represents a global measure of venous
drainage from unspecified cranial compartments
Imaging demonstrated substantial hypoxic
regions within the cerebral parenchyma that were
invisible to Sjvo2
Accurate measurement using jugular oximetry
requires continuous adequate flow past the
catheter.
Low- or no-flow states such as profound
hypoperfusion or complete ischemia render Sjvo2
unreliable
59. NIRS
Human skull is translucent to infrared light
Regional hemoglobin oxygen saturation (rSo2)
may be measured noninvasively with transcranial
near-infrared spectroscopy (NIRS)
NIRS measures all hemoglobin,pulsatile and
nonpulsatile, in a mixed microvascular bed
composed of gas-exchanging vessels with a
diameter less than 100 μm.
The measurement is thought to reflect
approximately 75% venousblood
60.
61. High baseline variability among subjects
Values < 50% considered low
Used to monitor trends
Fall of more than 20% especially if prolonged has
been associated with neurologic injury
Has been used during cooling to achieve 95%
value signifying maximal metabolic supression
Value keeps on decreasing during DHCA and
decay is faster at higher temperatures
62. NIRS during DHCA
During DHCA value decreases to a nadir of about
70% of baseline over 20-40 mins
At this point apparently there is no additional
uptake by neural tissue
Interestingly the time of this plateuing
corresponds to maximum duration of DHCA found
out by the studies i.e 40 mins
63. Uses
Used as transfusion trigger
Guide to supplemental cerebral perfusion
Defines limits of autoregulation
Anesthetic adequacy
67. EEG
To establish electrical silence before onset of
DHCA
Temperature range differs
Only signifies loss of impulse conduction and tells
nothing about baseline metabolism
Difficult to interpret,interference
BIS monitoring in some cases is reported to
detect cerebral hypoperfusion & cerebral air
embolism
70. Alternative strategies
DHCA is not free from ischemic complications
To counter this many perfusion strategies have
been developed which include
intermittent cerebral perfusion
low flow cardiopulmonary bypass
regional cerebral perfusion(ACP& RCP)
71. Intermittent low flow perfusion
systemic recirculation for 10-minute periods every
20 minutes during DHCA to prevent cerebral
anaerobic metabolism during long periods of
circulatory arrest.
This strategy is utilized commonly during
pulmonary thromboendarterectomy
This technique is not necessarily an alternative to
ACP and RCP
72. Low-flow Cardiopulmonary
Bypass
low-flow CPB was superior to DHCA with respect
to high-energy phosphate preservation, cerebral
oxygen metabolism, CBF, cerebral vascular
resistance, and brain lactate levels.
The minimum safe level of blood flow has not
been established
For infants, a minimal cerebral perfusion pressure
of 13 mm Hg was necessary to maintain flow, and
flow rates of about 50 mL/kg/min were required
73. Retrograde cerebral perfusion
RCP is performed by infusing cold oxygenated
blood into the superior vena cava cannula at a
temperature of 8° C to 14° C via CPB
The internal jugular venous pressure is
maintained at less than 25 mm Hg to prevent
cerebral edema
Site proximal to the superior vena cava perfusion
cannula and zeroed at the level of the ear
74. Patient is positioned in 10 degrees of
Trendelenburg
To Decrease the risk for cerebral air embolism
and prevent trapping of air
Flow rates of 200 to 600 mL/min usually can be
achieved
75. Advantages
The technique provides the opportunity for
thorough deairing of vessels of the arch.
Cerebral cooling is facilitated and toxin removal
occurs.
It may also remove solid emboli from the arterial
branches of the arch.
Avoids manipulation of the atheromatous arch
vessels and it allows removal of some cannulae
from the surgical field
The technique of DHCA with RCP is a reasonable
approach for neuroprotection during aortic arch
surgery in the setting of adequate institutional
experience (ACC/AHA Class IIa recommendation;
level of evidence B
76. Disadvantages
The disadvantages include the scanty evidence
that blood reaches the cerebral target, an
assumption that may provide false confidence.
During RCP, only a minimal amount of blood (not
more than 3% to 10%) is directed to the brain,
whereas more than 90% is deviated through the
azygos to the SVC or entrapped in the cerebral
venous sinuses
79. Anterograde cerebral perfusion
Perfusion of brain with oxygenated blood
independently of the rest of the body
At physiological flow and pressure of 10-20
mL/kg/min and >50 mm of Hg
Potential to prolong the safe time of circulatory
arrest
Improved cerebral cooling due to heterogeneous
flow, and its potential application with moderate
instead of deep hypothermia
80. Non selective cerebral perfusion
Non-selective ACP (NSACP), or hemispheric
perfusion, refers to selective cannulation of the right
axillary artery with lefthemispheric perfusion
dependent on a patent Circle of Willis
Advantages of axillary artery cannulation include its
use as an access for conduct of CPB and the relative
freedom of the axillary artery from dissection and
atherosclerotic disease, thus, decreasing the
incidence of atheroemboli.
Potential complications of axillary artery cannulation
include insufficient flow, inadequate right upper limb
perfusion, lymphocele, and brachial plexus injury
Perfusion of both hemispheres is compromised in
cases of absent communication at the Circle of Willis,
which can be present in up to 20% of patients
82. Selective anterograde cerebral
perfusion
Canulation of carotid artery and the innominate
artery, either directly or through a tube graft.
The drawbacks of this approach include the
needed dissection of these key vessels
May lead to vessel injury or embolization and the
inconvenience of added cannulae in the operative
field