1. Hypothermia and DHCA Abhi mishra Moderator: Dr Aveek
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)
4. VO2 vs temperature
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. Degrees of hypothermia Mild : 32-34 C Moderate : 25-32 C
Deep : 14-25 C Electrical silence : 12-18 C
7. possible sites of action Decreased excitotoxicity Decreased
necrosis and apoptosis Decreased microglial cell activation
Oxidative stress modulation Decreased inflammation post
ischemia
8. ExcitotoxicityIschemia:ATP depletion which leads toloss of
ion gradients and accumulationof intracellular K+ and Na+ Glutamate
release and decreased uptake Excessive Ca+ influx and cellular
hyperexcitability
9. Late consequences Cytotoxic edema Vasogenic edema
Dysfunctional BBB : increased interstitial water movement and rise
of pericellular hydrostatic pressure
10. Necrosis and apoptosis Hypothermia decreases cytochrome c
release Decrease caspase activation,DNA fragmentation
11. Decreased microglial activation Less production of IL-6 and
NO Inhibition of glutamate induced NO synthesis Supression of
neutrophil accumulation
12. 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
13. All acids and bases, including water, exist insolution in
equilibrium between the undissociatedform and the ionized
components of the parentmolecule. The dissociation constant (K) is
theequilibrium ratio of the product of theconcentrations of the
ionized components to theunionized component. For water at 25C,
theequilibrium dissociation equation is as follows:
14. 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 15C to 40C), 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 15C to 170
nmol/L at 40C
15. 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
16. Blood buffers At normal body temperature (37C), 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
17. 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
18. Ectothermic animals pH strategy
19. 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
20. 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 -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
21. 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
22. 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
23. 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
24. 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
25. 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
26. 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 26C 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
27. DHCA The most dramatic application demonstrating the
protective effects of hypothermia is in DHCA. Systemic temperatures
of 20C to 22C 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
28. 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
29. 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
30. Degree of hypothermia required Approximately 60% of the
brains energy consumption is used to transmit nerve impulses; the
remaining 40% is used for preservation of cellular activity.
Electrocerebral silence occurs at about 17C 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
31. 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
32. 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 13C 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
33. 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
34. Duration of DHCA
35. 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 7C May result in
brain hyperthermia during rewarming Perfusate temperature should
not exceed core body temperature by more than 10C; to stop
rewarming when core body temperature is 36C (esophageal) or 34C
(urinary bladder) and for perfusate temperature not to exceed 36C
Relative hypothermia (36C, esophageal; 34C, 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
36. 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
37. Cerebral blood flow determinats
38. Alpha or ph stat Acid-base management may be critical in
the setting of deep hypothermia. Proponents of the -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.
39. 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
-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
-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
40. Alpha or ph stat -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 -stat management was employed Cerebral
autoregulation was abolished and CBF varied with perfusion pressure
when pH-stat strategy was used
41. pH stat Alpha stat
42. 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
43. 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
44. Metabolic supression andrecovery
45. Targets for pharmacological protection
46. Pharmacological adjuncts
47. 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
48. Monitoring Standard ASA monitoring Arterial catheter
Pulmonary artrey cath if indicated TEE Jugular bulb oximetery and
temperature NIRS Trans cranial doppler EEG,BIS SSEP
49. TEE Cardiac function before and after DHCA Examination of
aorta Confirming canula placement Assesing volume status
Determining adequeacy of repair Detecting intra cardiac air
50. 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
51. 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%
52. 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
53. 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 m. The measurement is thought to reflect approximately 75%
venousblood
54. 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
55. 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
56. Uses Used as transfusion trigger Guide to supplemental
cerebral perfusion Defines limits of autoregulation Anesthetic
adequacy
57. Trans cranial doppler
58. Other usesCan also be used to calculate CMRO2 in
conjunction withSjVO2
59. 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
60. Multi modality neurophysiologicmonitoring
61. 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)
62. 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
63. Low-flow CardiopulmonaryBypass 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
64. 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
65. 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
66. 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
67. 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
68. Circuit in RCP
69. 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
70. 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
71. Non selective anterograde perfusion
72. Selective anterograde cerebralperfusion 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