14.5.3 Deep hypothermia and circulatory arrest

Lowering cellular metabolism through cooling offers the organs a certain degree of protection and enables ischaemia time to be prolonged for a variable period depending on the temperature. Due to this reduction in requirements, it is possible to lower the perfusion flow rate, which offers undeniable benefits.
 
  • Reduction of haematological trauma;
  • Reduced collateral flow and pulmonary venous flow in the operating field;
  • Option of discontinuing CPB for a short period or even remove some cannulas, which enables an improvement in the quality of surgical reconstruction in an immobile and blood-free operation field;
  • Reduced myocardial rewarming following cold cardioplegia (4°C);
  • Safety margin in the event of incidents requiring the CPB to be suddenly reduced or stopped.
The significant haemodilution required to slow the increase in blood viscosity due to the cold results in severe cellular oedema in immature hearts and lungs – their compliance is reduced. Hypothermia, which may be minor (30-34°C), moderate (23-30°C) or deep (15-22°C), has repercussions on numerous systems (Table 14.13) (see Chapter 18 - Cerebral Effects of Hypothermia). While it offers safer conditions for correcting complex heart diseases, but it is equivalent to normothermia (≥ 34°C) for simple heart diseases [36].


Deep hypothermia

Cellular metabolism decreases exponentially with the temperature – it falls by 7% per degree C. At 18°C, the cerebral O2 requirement (CMRO2) is 40% of its value at normothermia [24]. The metabolic reduction coefficient per 10°C decrement (Q10) is a mean value of 2.5 in adults and 3.65 in neonates [25]. Besides reducing VO2, hypothermia preserves high-energy phosphates and impedes the entry of Ca2+ into cells, although it causes Ca2+ to be released from the sarcoplasmic reticulum. This increase in [Ca2+]i may result in stone heart, prompting post-CPB ventricular failure. The resulting vasoconstriction is most pronounced in the muscles of the limbs and slightly less pronounced in the kidneys and splanchnic system (see Chapter 7 - Hypothermia). Once the metabolism is reduced, it is possible to lower the CPB blood flow based on blood temperature, although consideration should be given to infants’ higher baseline metabolism compared to adults (8-9 mL O2/kg/min versus 4 mL O2/kg/min at 37°) and VO2 reduction related to anaesthesia [34].
 
  • ≥ 34°C     2.5 L/min/m2
  • 32°          2.2 L/min/m2
  • 30°          2.0 L/min/m2
  • 28°          1.8 L/min/m2
  • 26°          1.6 L/min/m2
  • 24°          1.4 L/min/m2
  • 22°          1.2 L/min/m2
  • 20°          1.0 L/min/m2
  • 18°          0.7 L/min/m2
Flow compatibility with the body's requirements is continuously monitored by SvO2 and ScO2, supplemented by blood-gas analysis and measurements of lactate levels every 30 minutes.

The relationship between cerebral blood flow (CBF) and cerebral metabolism (normal CBF/CMRO2: 15/1) changes at low temperatures, with CBF becoming luxuriant (ratio of 60/1) [31]. In normocapnia, autoregulation of cerebral blood flow is maintained during moderate hypothermia (25-30°C) at mean arterial pressure levels of 50 mmHg. It is lost during deep hypothermia (< 23°C). In such instances, cerebral perfusion becomes pressure-dependent [12], although the CPB flow rate can be reduced as low as 10 mL/kg/min at 18°C before metabolic requirements are in deficit [20,21]. The lower temperature limit tolerated by the brain is probably 12°C, provided that hypothermia is homogeneous [20,22]. Below this value, the ions are able to diffuse according to their electrochemical gradients due to the inhibition of active membrane transfers (Na+/K+ and Na+/Ca2+ pumps), which causes progressive and irreversible intracellular oedema [30]. The most reliable clinical measurement of cerebral temperature is a tympanic or nasal probe (placed in contact with the ethmoidal sinuses). 

Circulatory arrest

When operating on complex malformations such as hypoplastic left heart syndrome requiring a blood-free operating field, ablation of cannulas, and correction of the aortic arch, low temperatures are used (15-18°C), enabling work to be performed during circulatory arrest. By lowering the metabolism, it is possible to discontinue cerebral circulation for a period of time. However, there is always a risk of neurological sequelae, irrespective of the temperature and duration – only the probability of irreversible lesions is quantifiable. This is illustrated by Figure 14.26, which summarises so-called “safe” durations of complete arrest according to temperature [22,23]:
 
  • 3-5 min at 37°C;
  • 12-15 min at 28°C;
  • 35-40 min at 18°C.


Figure 14.26: Nomogram showing estimated probability of full neurological recovery following total circulatory arrest at three different cerebral temperatures [20,23].

These durations are measured up to the point at which the curve bends, when the probability of neurological sequelae significantly increases. However, this is merely a probability – it is never zero and any prolongation of the duration increases the risk. The main operations during which deep hypothermia and circulatory arrest are normally applied are: total anomalous pulmonary venous return, Norwood, hemi-Fontan, arterial switch with VSD and interruption of the aortic arch [29].

Cerebral perfusion

A continuous low flow rate during deep hypothermia is a compromise aimed at maintaining the required supply for minimal cell function, preventing the accumulation of acid metabolites, and eliminating reperfusion lesions. Compared to total circulatory arrest, deep hypothermic low-flow ensures fewer immediate neurological complications (OR - 11.4) [26] and improved subsequent cognitive development [2,5]. However, many comparative studies show no significant difference between moderate hypothermic continuous low-flow and deep hypothermic total circulatory arrest [11,16]. It is difficult to determine the best strategy, since approaches differ between centres [34]. However, any protocol is effective if it is applied rigorously by a well-organised team that is fully familiar with it.

Metabolic requirements are theoretically met by a cerebral flow rate of 10-12 mL/kg/min at 15°C [8]. The brain can be selectively perfused by a cannula in the brachiocephalic trunk in order to protect it with continuous low flow during the circulatory arrest phase required for cardiac reconstruction. The right carotid artery is directly perfused and connexions with the external carotid system and the circle of Willis perfuse the left hemisphere [28]. Depending on the temperature, flow rates of 20-50 mL/kg/min are used at mean pressures of 20-40 mmHg. Since cerebral autoregulation is lost below 20°C, cerebral blood flow becomes linearly dependent on pressure at these temperatures. However, it drops suddenly to zero if the pressure falls to values of 11-15 mmHg [32]. It is therefore important that pressure is kept above these values. Moreover, jugular venous pressure must be zero otherwise it compromises the cerebral blood flow [13].

Technical aspects

Cooling by CPB is very gradual. To ensure homogeneity, it must be slow – ideally at least 20 minutes should be allowed to reach 20°C [3]. The level of neuromuscular blockade and the depth of anaesthesia must be sufficient to prevent shivering and minimise any peripheral oxygen requirement (VO2). During CPB, curarisation is likely to reduce overall VO2 by 10-30% [19]. Using vasodilator agents and pH-stat regulation helps ensure steady cooling and prevent the emergence of temperature gradients. Optimal haematocrit is 24%. A number of recommendations apply to temperature management during CPB [10].
 
  • The temperature gradient between the heat exchanger water and the blood must never exceed 10°C and the water temperature must not exceed 38° or fall below 12°C.
  • During cooling, the temperature gradient between the heat exchanger inlet and outlet must never exceed 10°C.
  • When the temperature is < 30°C during rewarming, the temperature gradient between the heat exchanger inlet and outlet must never exceed 10°C.
  • When the temperature is > 30°C during rewarming:
    • The temperature gradient between the heat exchanger inlet and outlet must remain ≤ 4°C;
    • The rewarming speed must remain ≤ 0.5°C/min.
  • Blood temperature at the heat exchanger outlet must never exceed 37°C to prevent cerebral hyperthermia.
  • The gradient between rectal/bladder temperature and oesophageal temperature must remain lower than 10°C – rectal or bladder T° is 2-4°C lower than brain temperature during rewarming.
In addition to hypothermia, a number of steps are taken to protect the brain in the event of circulatory arrest (see Cerebral Protection).
 
  • External cooling with crushed ice, which is packed around the child's head and neck. The temperature of the operating theatre is lowered to 16°C until rewarming.
  • Although the Trendelenburg position prevents air embolism if vessels are open or being manipulated, it increases venous pressure and may reduce effective cerebral perfusion pressure (Partery - Pvein) if it is too deep.
  • Normoglycaemia – hypoglycaemia entails greater risk for young children. It is advised to adjust blood glucose levels to 6-10 mmol/L prior to arrest.
  • Steroids: methylprednisolone reduces perifocal oedema due to its stabilising effect on the cell membranes [1]. Although it is unlikely to be effective for managing ischaemia, a single dose is safe, even at high dosage, and can therefore be justified for prophylaxis as it reduces the intensity of the inflammatory response [35]. The dose is 10-20 mg/kg administered 45 minutes prior to arrest.
  • Mannitol: it reduces cerebral oedema and helps improve parenchymal perfusion – it can be used to reduce reperfusion lesions due to its ability to capture free radicals [37]. It is administered 20-30 minutes prior to arrest at a dose of 0.5 g/kg.
  • Magnesium: as a sulphate or chloride, it has a powerful calcium channel-blocking effect and improves neurological recovery according to some studies [33]. The dose is 5-10 mmol 5 minutes prior to arrest.
  • pH-stat regulation during the cooling and rewarming phases [4,9,18].
  • Relatively high haematocrit should be maintained (> 24%) [16].
Barbiturates lower CMRO2 by 30% and improve focal lesion recovery, but not global cerebral ischaemia recovery [27]. However, embolic focal lesions are rarer than global ischaemic sequelae in young children. Moreover, barbiturates’ haemodynamic effects are prohibitive. Consequently, these agents are not used for cerebral protection in children.

There is no clear evidence to suggest that the various prophylactic methods mentioned here are able to significantly alter cerebral recovery. Only hypothermia and arrest brevity have a proven impact on long-term neurological outcomes.

Rewarming

During rewarming, the temperature gradient between the heat exchanger inlet and outlet must never exceed 10°C while the temperature is < 30°C. Once it is > 30°C, the temperature gradient must remain ≤ 4°C and the rewarming speed must remain ≤ 0.5°C/min. Moreover, blood temperature at the heat exchanger outlet must never exceed 37°C [10]. The artery-oesophagus temperature gradient must remain at 2-3°C [7]; However, the drawback of this gradual rewarming process is prolonged CPB duration [15].

If rewarming is performed rapidly, the brain becomes dangerously hyperthermic (38-39°) for several hours [6]. Indeed, since it is one of the most generously perfused organs, its temperature changes faster than body temperature. This phenomenon profoundly exacerbates the neurons’ susceptibility to ischaemia and increases the extent of focal lesions. It limits the efficacy of autoregulation and makes the cerebral blood flow more pressure-dependent. Neurological sequelae are also proportionate to the rewarming speed and to the fall in jugular venous saturation during rewarming [14,15]. A drop in cerebral O2 saturation (ScO2) indicates an imbalance between the O2 requirement and the cerebral blood flow. Cerebral hyperthermia is responsible for 50-75% of neuropsychological complications whose severity is directly linked to the rewarming speed [17].

 
Hypothermia
Hypothermia reduces tissue metabolic requirements (7%/°C reduction for the brain), enables the CPB flow rate to be reduced (1.8 L/min/m2 at 28°, 1.0 L/min/m2 at 20°), and allows it to be discontinued temporarily. Duration of circulatory arrest considered as safe:

­     - 3-5 minutes at 37°C
­     - 15 minutes at 28°C
­     - 40 minutes at 18°C

On rewarming, a rebound effect causes cerebral hyperthermia, which is very harmful. Maximum rewarming speed: 1°/2-4 min; gradient between the heat exchanger and rectal T°: < 10°C; Blood T°: ≤ 37°C.

Cerebral protection measures:
­    - Continuous selective perfusion
­    - Hypothermia at 18-20°C, steady and slow cooling and rewarming (1°/3-4 min), risk of cerebral hyperthermia on rewarming
­    - Moderate hypothermia (28-30°C), continuous cerebral + splanchnic perfusion by right subclavian and femoral cannulation
­    - Trendelenburg position
­    - Normoglycaemia, mannitol (↓ cerebral oedema)
­    - Deep anaesthesia (curarisation)
­    - Unproven: Mg2+, thiopental, nimodipine, methylprednisolone
    
 
© BETTEX D, BOEGLI Y, CHASSOT PG, June 2008, last update February 2020
 
 
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