Brief notes on hypothermia, dhca, rcp,acp,sacp & oxygen requirement. for Perfusionist & Perfusion students..

1. HYPOTHERMIA, DHCA
COOLING,REWARMING
O2&CO2 CONSUMPTION
-Karthi murugan

2. 2

3. • Hypothermia
– HYPO - Under
– THERMIA - State of heat
3
The condition of having an abnormally (typically
dangerous) low body temperature.

4. • Hippocrates, the ancient Greek physician, was
the first to recognize the benefits of
hypothermia, advocating that wounded
soldiers can be covered with snow or ice
• Larrey,(france) use of ice on injured soldieers
• William Osler, another great physician, placed his typhoid
fever patients in a cold bath in the 1890s
• In 1950, Bigelow (canada) first demonstrated the linear
relationship between falling temperature and falling
metabolic rate when anaesthesia was used to control
shivering and the increased muscle tone generated in
response to cold
HISTORY
4

5. • In 1952, Lewis & Taufic used surface cooling to 28°C
with 5.5 minutes of inflow occlusion to facilitate
successful closure of an atrial septal defect in a 5-
year-old child
• These findings were applied by Lewis et al. during
their first open intracardiac repair in 1953
• Hypothermia equipment, used at the University of
Colorado Medical Center in 1953, is in the
Smithsonian Institution in Washington, D.C., as a
medical “landmark”
• 1953 Swan (US)Experimented with hypothermia
further, and used this knowledge to the success of
his first open-heart surgery. Swan went on to use this
on hundreds of patients, with low mortality
5

6. • 1955 Cooley (US) First use of hypothermia for
cerebral protection during first aortic arch aneurysm
repair with a homograft
• 1955 Lillehei and Kirklin (US) Noticed and published
that better outcomes occurred when body
temperature cooled spontaneously during
oxygenation
• After the development of the pump oxygenator by
gibbon, CPB and hypothermia were combined by
Sealy in 1958, and some degree of hypothermia
became common practice in the conduct of cpb
• 1959 Sealy (US) Continued Lillehei and Kirklin's
development and added a heat exchanger to a
DeWall oxygenator to use hypothermia alongside it 6

7. • 1959 Drew (England) First employed his own technique to
use the patient's lungs instead of an oxygenator alongside
hypothermia, and went on to apply this throughout his
surgical career
• 1960s Meshalkin (Russia) Used ice and snow to operate
without cardiopulmonary bypass
• 1963 Barnard and Schrire (South Africa) First used DHCA and
CPB at the same time on an ascending and arch aortic
aneurysm
• 1964, Peter Safar – at the University of Pittsburgh physician
who is credited with pioneering cardiopulmonary
resuscitation – actually included hypothermia in his
recommendations for what doctors should do after
successfully restarting a patient’s heart – 1959 Baltimore??
• 1975 Griepp (US)Used surface cooling with CPB to resect
aortic arch aneurysms in four patients
7

8. –Regulated in the hypothalamus
• The hypothalamus is the body’s
“thermostat”
• The hypothalamus works as a
regulator for shivering and
sweating, depending on the
environmental stimulus (excessive
cold or heat)
• The body has thermo sensors in
the skin the mucosa, and in
certain deeper structures in the
body
Temperature regulation:
8

9. • Normal body temperature is 98.6
o
F or 37
o
C
• There are two rates the temperature regulation
system effects:
Basal Rate- the normal resting rate for the CORE of the
body ( Deep internal temperature i.e, the metabolism
that occurs when the body is completely at rest)
Metabolic Rate- reactive adjustment to the
environment to maintain a continual core temperature,
i.e, the body continuously adjusts the metabolic rate in
order to maintain a constant CORE temperature
9

10. 10

11. Common measurement site
• Core Sites
– Pulmonary artery
– Distal esophagus
– Nasopharynx
– Tympanic membrane thermocouple
– Rectal
• Other generally-reliable sites
– Mouth
– Axilla
– Bladder
• Sub-optimal
– Forehead skin
– Infrared “tympanic”
– Infrared “temporal artery” 11

12. 12

13. Key findings at different degrees of hypothermia
13

14. 14

15. HYPOTHERMIA
15
Hyperpyrexia >40.0 or 41.5 °C

16. Mechanisms of action
The effect of hypothermia on the brain is complex
and not fully understood. It has been established that
induced hypothermia has the following mechanisms of
action that lead to its neuroprotective effect:
Reduction in cerebral metabolism (CMRO2) by
approximately 7% per 1°C. This leads to less oxygen and
glucose consumption.
Promotion of cerebral vasoconstriction, which can
directly decrease ICP. Also vascular permeability and
therefore oedema formation is decreased.
Prevention of neuronal injury leading to programmed
cell death (apoptosis) mainly by inhibition of caspase
activation.
16

17. Suppression of the inflammatory cascade and
decreased nitric oxide, cytokine and leukotriene
production. Leukocyte migration from the damaged
endothelium is diminished.
Improved ionic homeostasis and blockage of the
destructive neuroexitotoxic cascade consequent to
glutamate accumulation and receptor activation, and
subsequent intracellular calcium overload.
Decreased free radical formation.
It allows for the cerebral regional temperature
differences of 2–3°C that are known to exist (cerebral
thermo-pooling). Thus, the likelihood of some areas
of the brain being hyperthermic (which is known to
worsen outcome) is reduced.
17

18. Physiology of hypothermia
• Core temperature is a reflection of the balance between heat production
and heat loss. Heat is produced because of breakdown of high-energy
phosphate bonds, and heat is lost through the lungs and skin. Radiation
heat loss from the body occurs primarily from infrared emission.
• In the initial stages of hypothermia, thermoreceptors situated in the skin
and subcutaneous tissues sense the low ambient temperature and cause
a regional vasoconstriction. This causes the hypothalamus to stimulate
the release of TSH and ACTH, leading to stimulation of thyroid and
adrenal glands. The hypothalamus also stimulates heat production by
promoting shivering, typically occurring between 34°C and 36°C (93.2°F
and 96.8°F). Owing to the effects of prolonged vasoconstriction, acidosis
may occur, which may blunt the response to catecholamine production.
18

19. • Continuous ECG monitoring demonstrates
generalised slowing of the heart rate followed by
T-wave inversion & prolongation of QT interval
• The respiratory center is stimulated, but as time passes, the
respiratory rate and tidal volume become depressed.
Anatomical and physiological dead space increases, as does
bronchiolar and alveolar oedema
• The renal blood flow and glomerular filtration rate decrease
as well. Tubular reabsorption decreases as this is an energy-
requiring process. As a result, cold-induced natriuresis and
diuresis occur.
• Hypothermia is also associated with insulin resistance and
hyperglycaemia. Platelet dysfunction commonly occurs and
may lead to a bleeding disorder. The vasoconstriction may
lead to tissue hypoxia and protein wasting
19

20. • The solubility of gases in biologic fluids increases with
hypothermia.
– At a constant CO2 content, PaCO2 decreases as temperature
falls
• Protection of the brain during deep hypothermia (temperature
<20°C) may be best accomplished with a mixed acid–base
strategy:
– pH-stat during the initial cooling phase
– Alpha-stat during reperfusion, rewarming, and termination
of cardiopulmonary bypass
– Alpha-stat regulation preserves the ratio of [OH–] to [H+] with
temperature change and produces an alkaline shift with
cooling
– pH-stat regulation maintains absolute a constant [H+]
regardless of temperature and requires added H+, usually as
CO2, with cooling 20

21. Beneficial Effects of Hypothermia
• Allows to decreases in pump flow rates, which facilitate surgical
exposure, decreased rate of myocardial rewarming, and some
protection to other organs during periods of CPB and low-flow states
• Decreases the tendency for weak acids and bases to dissociate in
solution.
• Causes a decrease in blood flow to all vascular beds in proportion to
the reduced metabolic demands.
• Allows proportionate reductions in CPB systemic flow guided by
nomograms that rely on plateauing of VO2.
• Ischemic neuronal cell repidly release neuroexcitatory
amines(glutamate)cause the opening of calcium channels and
activation of multiple destructive enzymatic system can be
controlled.
21

22. • Decrease in cerebral metabolism
• Maintains integrity of membranes
• Preserves ion homeostasis
• Decreases excitatory AA release
• Decrease Ca influx
• Decrease lipid peroxidation
• Decrease free radical formation
• Decrease nitric oxide synthase activity
22

23. DHCA
• Complex arch & congenital surgeries
• Safe – short arrest durations
• > 25 min -  transient neurological
deficits(>20 %)
• > 40 min -  stroke(>5-7%)
23

24. 24

25. 25

26. DURING DHCA
26

27. TECHNIQUE OF DHCA
• Usually planned - Haemodilution - Corticosteroids
• Reduce water bath and cool gradually until the desired
temperature
• Keep informed and have wide communication with
anaesthetist and surgeon
• The cooling phase should be atleast 30 min and thoroughly,
and long enough to achieve homogenous allocation of blood
to various organs and to prevent a gradual updrift of
temperature during DHCA.
27

28. • During cooling, pump flow should be restored at levels of
2.2–2.4 L/min/m2 with a “temperature gradient”(blood -
nasopharyngeal) not exceeding 10°C
• Keep ph stat on cooling
• Rapid cooling might create imbalance between oxygen
delivery and demand, and it might decrease oxygen
availability to the tissues 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
• Ice packing of the skull enhances cerebral hypothermia via
conduction across the skull ( make sure no frost bite) 28

29. • Arterial pump head is stopped and arterial line is clamped and
Whole blood volume of patient is drained into venous reservoir until
level stop rising and line clamped
• Recirculation line is unclamped and recirculation is begun through
the oxygenator ( with temp of patient, CUF, Bicarb)
• Keep informing the time with temperature
• Once the arrest period is over, the arterial pump head is stopped and
recirculation line is clamped
• Arterial line is unclamped and arterial pump is started
• Perfusate (blood) is transfused back into the patient to re establish
circulating volume
• Venous line is unclamped and cardiopulmonary bypass is reinstitued
29

30. 30

31. 31

32. 32
Retrograde cerebral perfusion was first described by Mills
and Ochsner in 1980

33. 33

34. 34

35. 35

36. 36

37. 37

38. 38

39. 39

40. 40

41. Direct Innominate Artery Cannulation for
Selective Antegrade Cerebral Perfusion
Circulatory arrest at 25 – 28’c
• Connect aortic line to ACP
cannula
• Clamp base of innominate
artery
• ACP Delivery @24’C
• Flow 10 – 12ml/kg/min
41

42. 42

43. Intermittent DHCA
• Use of intermittent hypothermic cerebral
perfusion for I to 2min at I5-20 min intervals
• In a piglet model of DHCA, 1 minute of
reperfusion for every 15 minutes of DHCA has
been found to be sufficient to provide normal
metabolic and microscopic cerebral recovery
• SjVo2
43

44. Low flow CPB - DHCA
• Cerebral protection is the most important time-
limiting factor during surgical procedures
necessitating DHCA and low-flow CPB. Swain et
al.
• Infants assigned to DHCA, as compared with
those assigned to low-flow CPB, had a higher risk
of delayed motor development and neurologic
abnormalities.
• The risk and severity of neurologic abnormalities
increased with the duration of DHCA
44

45. 45

46. 46

47. COOLING
47
1. CORE COOLING with ECC.
2. SURFACE COOLING with water blankets kept under/over patient.
3. Surface cooling with ECC
4. Other methods -external ice on heart and ice packs on head.
Cooling rates should be less than 1’c / min

48. 48

49. 49

50. Rewarming
• Rapid rewarming can harm cerebral cells and induce
neural damage.
– It can achieved using a number of different
methods
• 1.Passive external rewarming.
• 2.Active external rewarming.
• 3.Active Internal rewarming.
50

51. 51
Passive external rewarming Active external rewarming Active Internal rewarming

52. • Rate of rewarming
• Maintain gradient of nasal to water bath of atleast 6’c
in adult and 4’c in paediatrics
• Warm at the rate of 1’c for 3-5 mins
• Never come down (except redo arrest) with the temp
setting by lowering the bath temperature if target
temperature exceeds
• Plan accordingly with surgeon , consulting with
anaesthetist.
• Consider - Bicarb, Mannitol, ZBUF, CUF
• Proper Gas flow
52

53. After drop
53

54. `
54

55. Oxygen
consumption
55

56. 56
In 1774, in England, Joseph priestley also discovered
Oxygen, unaware that Scheele had same experience.
Most often it is Priestley who receives credit for
Discovering oxygen.

57. 57

58. 58

59. OXYGEN CASCADE THEORY
• Oxygen moves down the concentration gradient from
a relatively high levels in air to that in the cell
• The PO2reaches the lowest level (4-20 mmHg) in the
mitochondria
59

60. Oxygen Transport
Carried in blood in 2 forms:
1. By red blood cells
– Bound to Hb
– 97-98%
2. Dissolved O2 in plasma
– Obeys Henry’s law
– PO2 x = O2 conc in sol
= Solubility Coefficient (0.003mL/100mL/mmHg
at 37C)
 Low capacity to carry O2
60
Bound to
Hb
97%
Dissolved
in 02
3%
O2 TRANSPORT

61. 61
Human hemoglobin has a molecular weight of 64,500

62. 62

63. 63

64. • Ratio of oxygen bound to Hb compared to
total amount that can be bound is Oxygen
Saturation
• Maximal amount of O2 bound to Hb is
defined as the Oxygen Capacity
• O2 CONTENT -
The sum of O2 carried on Hb and
dissolved in plasma CaO2 (ml/dL) = (SaO2 x
Hb x 1.34) + (PO2 x0.003)
64

65. Factors affecting oxygen transport
At least seven mechanisms could potentially
affect the transport and utilization of oxygen during
hypothermia:
Changes in the metabolic rate,
Changes in the solubility of oxygen,
Acid–base strategy,
Changes in the oxygen– hemoglobin dissociation
curve,
Changes in the cardiac output or CPB flow,
Changes in the concentration of hemoglobin,
 Changes in the “critical pO2”. 65

66. • Q10 defines the ratio of oxygen consumption at a defined
temperature to the oxygen consumption at temperature
10◦C lower
Multiple by which the rate of reaction decreases for
every 10°C
Q10(infants) – 3.65
Q10 (adults) – 2.6
whereas cerebral Q10 is approximately 2.1–3.5
• Infants have greater metabolic supression with hypothermia
• Higher Q10 suggests a greater metabolic suppression related
to hypothermia
– Better ability to tolerate longer periods of “imperfect”
perfusion
66

67. P50
• The partial pressure of oxygen in the blood at which
• the haemoglobin is 50% saturated, is known as the
P50.
• The P50 is a conventional measure of haemoglobin
• affinity for oxygen
• Normal P50 value is 26.7 mm Hg
• As P50 increases/decreases, we say the “curve has
shifted”.
– P50 less than 27: Shift to the left.
– P50 greater than 27: Shift to the right.
67

68. 68

69. Factors affecting Dissociation
• BLOOD TEMPERATURE
• • Increased blood temperature
• • Reduces haemoglobin affinity for O2
• BLOOD Ph
• • Lowering of blood pH (making blood more acidic)
• • Caused by presence of H+ ions 4m lactic acid or carbonic acid
• • Reduces affinity of Hb for O2
• CARBON DIOXIDE CONCENTRATION
• • The higher CO2 concentration in tissue
• • The less the affinity of Hb for O2
69

70. 2,3 DPG(diphosphoglycerate)
70
2,3 DPG is an organic phosphate normally
found in the RBC Produced during
Anaerobic glycolysis in RBCS

71. 2,3 DPG
• Tendency to bind to β chains of Hb and
thereby
decrease the affinity of Hemoglobin for oxygen.
• HbO2 + 2,3 DPG → Hb-2,3 DPG + O2
• It promotes a rightward shift and enhances
oxygen unloading at the tissues.
• This shift is longer in duration than that due
to [H+], PCO2 or temperature.
• – A doubling of DPG will result in a 10 torr
increase in P50.
71

72. • The levels increase with
– Cellular hypoxia.
– Anemia
– Hypoxemia secondary toCOPD
– Congenital Heart Disease
– Ascent to high altitudes
The levels decrease with
– Septic Shock
– Acidemia
– Stored blood ( No DPG after 2 weeks of storage)
72

73. OXYGEN STORES
• O2 stores are limited to lung and blood.
• The amount of O2 in the lung is dependent on
the FRC and the alveolar concentration
ofoxygen.
• Breathing 100% oxygen causes a large increase
in the total stores as the FRC fills with oxygen
• This is the reason why pre-oxygenation is so
effective.
73

74. Factors affecting extraction ratio of
oxygen from capillary blood
• Rate of oxygen delivery to the capillary
• Oxygen-haemoglobin dissociation relation
• Rate of use of oxygen by cells
• Size of the capillary to cellular PO2 gradient
• Diffusion distance from the capillary to the
cell
74

75. 75

76. FACTORS NEEDING TO BE MAINTAINED TO
PREVENT TISSUE HYPOXIA
• Oxygen saturation
• Cardiac output
• Haemoglobin concentration
• Oxygen release from haemoglobin
• Extracellular diffusion
• Oxygen use by cells
76

77. Tolerance to hypoxia of various
tissues
Tissue Survival time
Brain <3 min
Kidney and liver 15-20 mins
Skeletal muscle 60-90 mins
Vascular smooth muscle 24-72 hrs
Hair and Nails Several days
77

78. Whole Body Oxygen Consumption as
a Function of Body Temperature
Temperature (°C) Oxygen Consumption (%)
37 100
32 60
30 50
28 40
25 25-30
20 20
10 10
78

79. 79

80. PHYSIOLOGY OF CO2 TRANSPORT
• End-product of aerobic metabolism.
– Production averages 200 ml/min in resting
adult
– During exercise this amount may increase 6x
Produced almost entirely in the
mitochondria.
• Importance of Co2 elimination lies in the fact
that -Ventilatory control system is more
responsive to PaCO2 changes.
80

81. • Carbon dioxide is transported in the blood
from the tissue to the lungs in 3 ways:
(i) dissolved in solution
(ii) buffered with water as carbonic acid
(iii) bound to proteins, particularly haemoglobin.
• Approximately 75% of carbon dioxide is
transport in the red blood cell and
25% in the plasma
attributable to
– lack of carbonic anhydrase in plasma
– plasma plays little role in buffering and
combination with plasma proteins is poor. 81

82. CARBON DIOXIDE DISSOCIATION CURVE
• Carbamino hb is much
affected by the state of
oxygenation of hb, less
so by the PCO2.
• Lower the saturation of
Hb with O2 , larger the
CO2 conc for a given
PaCO2
• CO2 curve is shifted to
right by increase in SpO2
82

83. 83

84. 84

85. 85

86. 86

87. Reference

88. 88