7.3.5 Hypothermia

 To reduce tissue oxygen consumption, a variable degree of cooling is commun in ECC: mild (32-35°C), moderate (28-31°C) or deep (< 25°C) hypothermia. However, this concept has been challenged over the last twenty years in favour of maintaining the temperature in the normothermic zone (35-37°C). Indeed, advances in bypass surgery technology now allow a high flow rate to be maintained without significant complications, whereas previously it was imperative to lower the flow rate to minimise haematological and tissue damage.

Benefits of hypothermia

Hypothermia affects many systems. Cellular metabolism decreases exponentially with temperature: it drops by 7% per degree centigrade. A cooling of 10° therefore reduces requirements by 50%. The benefits of hypothermia are numerous (Table 7.3).

• Reduction of pump flow (less bleeding in the operating field, less haemolysis); 1.5 L/min/m² is sufficient to cover the body's needs at 25°C.
• Improved myocardial protection.
• Improved brain protection.
• Reduction of trauma to the blood elements and proteins.
• Reduction of the inflammatory reaction.
• Reduction in the need for allologous blood.

However, hypothermia also has its drawbacks [13].

• Increase in blood viscosity, compensated by a decrease in haematocrit; in hypothermia, viscosity remains approximately stable when Ht in % has the same value as temperature in °C.
• Increased systemic arterial resistance and peripheral vasoconstriction.
• Catecholamine secretion, insulin resistance.
• Functional alterations of proteases of the coagulation cascade.
• Reversible inhibition of platelet adhesion (but preservation of aggregation).
• Leftward shift of the Hb dissociation curve (decreased availability of O₂ to the tissues).
• Prolongation of the effect of administered substances (decreased clearances, increased solubility of gases).
• Temperature non-uniformity; organs with high perfusion (brain, kidneys, heart) change their temperature more rapidly than the rest of the body.
• Need to rewarm the patient and risk of hyperthermia, especially the brain.
• Risk of secondary drop of body temperature (afterdrop).

The metabolic rate of decline per 10°C (Q₁₀ ) varies between temperatures, species, organs and ages. In humans, the overall value is 2, i.e. the metabolism decreases by half for every 10°C drop. The decrease in cellular metabolism in cold temperatures allows the duration of ischaemia to be extended by a variable amount depending on the organ. As the brain is the most sensitive structure, the possible ischemia time depends on its own tolerance. At 18°C, the O₂ consumption of the brain (CMRO₂ ) is 40% of its value in normothermia [20]. Whereas anaesthetic agents only modify electrical activity, hypothermia allows a decrease in the cellular metabolism of neurons (40% of the CMRO₂ ) as well as in their synaptic activity (60% of the CMRO₂ ) [20,30]. For the brain, the decrease in Q₁₀ between 37° and 27° is due to the reduction in metabolic activity, but the more rapid decrease in CMRO₂ between 27° and 18°C (Q₁₀ increased) is attributed to the suppression of electrical activity [21]. The EEG is isoelectric below 20°C. The lower limit of temperature tolerated by the brain is probably 12°C, provided that hypothermia is uniform [19]. Below this value, inhibition of membrane ion pumps allows ions to diffuse along their electrochemical gradients, leading to progressive intracellular oedema [27].

The coupling between blood flow (CBF) and metabolism (normal CBF/CMRO ratio₂ : 15/1) changes with cold: at low temperatures, the CBF becomes luxuriant (ratio 30/1). Selfregulation of cerebral blood flow is partially preserved in moderate hypothermia (25-30°C) for mean arterial pressure regimes of 50-80 mmHg and normocapnia, but is lost in deep hypothermia (< 25°C). Selfregulation is most impaired during the rewarming phase and the postoperative stroke rate appears to be directly related to this impairment (odds ratio 6.57) [18]. However, it should be borne in mind that these temperatures may be inhomogeneous; intracerebral gradients may exist, for example between the cortex and the bulb. On the other hand, the location of the measurement is important; the most reliable locations are the jugular bulb (retrograde jugular catheter), the eardrum (foam probe) or the ethmoidal cells (probe inserted through the nose until it reaches the nasopharynx). 

Cooling and heating

Systemic cooling through ECC is effective but not uniform. Organs with preferential perfusion (heart, brain, liver, kidneys) cool and warm rapidly, but organs with low blood flow to tissue mass ratios (fat, skin, muscle) change their temperature more slowly. Thermal gradients therefore take place, which can be assessed by measuring two different temperatures.

• Esophageal temperature, which represents the high perfusion organs, but is influenced by a cooled heart ;
• Rectal or bladder temperature, which represents organs with an intermediate blood flow/tissue mass ratio;
• To monitor brain temperature, a probe is placed against the eardrum or against the ethmoidal cells (nasopharyngeal T°); the latter is more reliable before weaning off bypass.
• The T° of the pulmonary catheter is reliable as soon as pulmonary flow is restored.

When cooling or rewarming, thermal gradients of more than 10° between oesophageal and rectal temperatures should be avoided, as this reflects too much inhomogeneity. In addition, dissolved gases change to the gaseous phase when the temperature rises sharply, which happens when warm blood passes through still cold tissue, or vice versa. Gaseous micro-embolisations are then formed, which can lead to capillary occlusions and areas of focal ischaemia.

There are a number of recommendations for temperature management during ECC [8].

• Temperature gradient between water in the heat exchanger and blood should never exceed 10°C, and water temperature should not go above 38°C or below 12°C.
• During cooling, the temperature gradient between the inlet and outlet of the heat exchanger should never exceed 10°C.
• During rewarming when the temperature is < 30°C, the temperature gradient between the inlet and outlet of the heat exchanger must never exceed 10°C.
• During warming up when the temperature is > 30°C:
  • The temperature gradient between the inlet and outlet of the heat exchanger must remain ≤ 4°C;
  • The heating rate should remain ≤ 0.5°C/min.
• Temperature of blood leaving the heat exchanger should never exceed 37°C to avoid cerebral hyperthermia.
• The gradient between rectal/vesical and oesophageal temperature should remain below 10°C; rectal or bladder T° is 2-4°C below brain temperature during rewarming.

On warming, the brain becomes transiently hyperthermic (38-39°) [4]. Because the brain is one of the best perfused organs and therefore its temperature changes more rapidly than the body during rewarmig. This thermal rebound is more pronounced the faster the warming. It profoundly increases the susceptibility of neurons to ischaemia and increases the extent of focal injury [17,23]. It decreases the efficiency of selfregulation and makes cerebral blood flow more pressure-dependent. Neurological sequelae are proportional to the speed of rewarming [10] and the fall in jugular venous saturation during rewarming [7]. A fall in cerebral O₂ saturation (ScO₂ ) indicates an imbalance between O₂ consumption and brain blood flow. Hyperthermia is responsible for 50-75% of type II neuropsychological changes, the extent of which is directly related to the rate of warming [10,12,14]. This should not exceed 1°C per 5 minutes, nor should the artery-oesophagus temperature gradient exceed 2-3°C [5,17]; however, this progressive rewarming extends the duration of ECC [11]. To avoid cerebral hyperthermia, the most appropriate approach is to focus on four points [11,31]:

• Avoid hypothermia during bypass surgery (T° min > 33°C);
• Heat up slowly (1°C/5 min);
• Maintain the T° of the blood at ≤ 37°C during rewarming (measured on the arterial cannula);
• Wean off from pump at 36° (core temperature).

The last point is highly debatable, as the temperature of the slightly hypothermic patient will drop in the first postoperative hours (afterdrop), since the insufficiently warmed muscle mass represents a cold reservoir that the patient will have to warm up by increasing cardiac output and shivering, conditions associated with a high risk of myocardial ischaemia and a extended extubation time [6]. These risks outweigh the potential benefits. The best compromise is therefore to warm the patient to 36° or 36.5°.

Monitoring brain temperature is challenging because no probe can measure the brain temperature itself, and is also not homogeneous. The three closest measurement points are the jugular venous blood (retrograde catheterisation of the jugular bulb), the eardrum (special foam probe) and the ethmoidal cells (standard nasopharyngeal probe pressed against the posterior-superior wall of the pharynx). Other sites (oesophagus, rectum, bladder, pulmonary artery) may have gradients of up to 5°C relative to brain temperature, and show a significant lag in thermal variation [11,24]. Arterial blood temperature at the heat exchanger outlet correlates best with jugular bulb temperature [8,24].

Temperature control: normothermia versus hypothermia

There is still a lively debate between the two attitudes, "warm" versus "cold" bypass surgery, because both techniques have a particular impact on different body systems [25,29]. Indeed, the benefits of hypothermia are indisputable in complex operations with long aortic clamps, and in circulatory arrest such as in aortic arch surgery. They are much less obvious in simple operations and in low-risk patients. They are also very different for different organs.

• Neuroprotection; hypothermia, even by a few degrees, improves cerebral oxygenation (measured by SvO₂ jugular or cerebral saturation ScO₂ ) and decreases neurological sequelae [3,31]; it is essential in case of circulatory arrest [32].
• Cardioprotection; cold cardioplegia inhibits myocardial metabolism and provides 30-50 minutes of protection which can be extended by iterative infusions.
• Kidneys and viscera; they do not appear to benefit from hypothermia [33].
• Coagulation; hypothermia alters the activities of coagulation chain proteins and platelet adhesiveness, but these changes are reversible on warming [36].

Normothermia or mild hypothermia (≥ 34°C) provides rather better results than moderate hypothermia (28°) in standard cases. It tends to be used for routine cases.

• Warm cardioplegia offers excellent protection provided that it is continuous or with only brief interruptions (< 12 minutes). Functional recovery of the myocardium after bypass surgery is better and faster than in hypothermia, the rate of spontaneous defibrillation is higher, and the incidence of atrial fibrillation or ventricular assist is halved [1,9].
• The impact on neurological risk is not clearly demonstrated, but there is probably no difference as long as perfusion pressure is properly maintained [25]. Stroke risk and cognitive dysfunction do not appear to differ, probably because the former is primarily embolic in nature and the latter is related to underlying brain pathology [28].
• There is no risk of hyperthermia on rewarming [14].
• The coagulation changes are less and the risk of bleeding is lower [37].

Acid-base balance

When cold, the solubility of gases in liquids increases. For example, the PCO₂ measured in a normal blood sample (PCO₂ 40 mmHg) cooled to 27°C is only 23 mmHg, even though no exchange with the outside has taken place, because the soluble fraction of the gas [HCO₃ ] has increased. At 20°C, the normal apparent pH is 7.7 and the PCO₂ is 18 mmHg. In clinical practice, acid-base regulation can be achieved by two techniques (Figure 7.25) [34].

Figure 7.25: Regulation of acid-base balance in hypothermia. In the α-stat mode, the total CO₂ content is kept constant, but the reading is taken in a device with the sample reduced to 37°, as if the patient were normothermic. As the solubility of the gas is increased when cold, the partial pressure is actually lower; the blood becomes artificially alkaline and hypocapnic, but the ratio [H⁺ ]/[OH^- ] remains constant. In the pH-stat mode, the pH of the blood is maintained at 7.4 regardless of temperature by adding CO₂ to the ventilated gas; the CO content₂ increases (apparent hypercarbia) and the pH falls. If the pH is maintained at 7.4 at 17°, the sample read at 37° gives a value of 7.08 (corresponding PCO₂ : 110 mmHg).

• In the alpha-stat mode, which is most often used, the total CO₂ content is kept constant, but the reading is taken in an apparatus in which the sample is reduced to 37°, as if the patient were normothermic. As the solubility of the gas is increased when cold, the partial pressure is actually lower; the blood becomes artificially alkaline and hypocapnic, but the ratio [H⁺ ]/[OH^- ] remains constant. In this situation, brain selfregulation is intact, extracellular acidosis is reduced, pHi is kept stable, and intracellular enzyme functions are fully preserved [35]. Most cold-blooded animals (poikilotherms) hibernate using this process because glycolysis, which produces little CO₂ , is sufficient to meet their low metabolic needs [34].
• In the pH-stat mode, the blood pH is maintained at 7.4 regardless of temperature by adding CO₂ to the ventilated gas; the CO content₂ increases (apparent hypercarbia) and the pH decreases. If the pH is maintained at 7.4 at 17°, the sample read at 37° gives a value of 7.08 (corresponding PCO₂ : 110 mmHg). This technique causes hypercarbic cerebral vasodilation which induces luxuriant perfusion and makes the flow pressure dependent [22]; selfregulation is lost, and the risks of cerebral oedema or embolisation are increased. In the Trendelenburg position, intracranial pressure can increase dangerously when venous pressure is high and the arterial vessels are maximally vasodilated.

The alpha-stat technique, which is simpler in practice, is used routinely for ECC in moderate hypothermia (25-30°C), as neurological outcomes at 6 weeks and 2 months are significantly better in these conditions [23,26,31]. In addition to shifting the Hb dissociation curve to the right, the pH-stat strategy has the advantage of doubling the cerebral blood flow (CBF). As this improves the homogeneity of cooling and rewarming, the pH-stat technique is probably indicated during cooling and rewarming of patients brought to a low temperature (< 25°), as it promotes rapid and uniform brain thermal changes, especially during complete circulatory arrest [2,16]. In situations where selfregulation is impaired such as diabetes, hypertension and history of stroke, the pH-stat technique is probably preferable as it better maintains cerebral oxygenation [15]. Note that selfregulation is ineffective below 25°C anyway. For ECCs of less than 90 minutes and temperatures above 30°C, the two techniques do not differ significantly.

Proteins behave as weak acids at the usual pH of blood and are a major buffer system in the acid-base balance. In contrast to the bicarbonate system, they maintain their buffering capacity intact at low temperatures because the degree of dissociation of the imidazole group of histidine does not change in relation to water as a function of temperature. In hypothermia, the acidosis must therefore be corrected by the addition of protein, because the buffering capacity of bicarbonate becomes ineffective below 28°C [34].

 © CHASSOT PG, GRONCHI F, last update December 2019

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