Whole-Body Cooling
Ela Chakkarapani
Marianne Thoresen
Moderate therapeutic hypothermia (HT; rectal or esophageal temperature 33.5°C) initiated within 6 hours of birth and continued for 72 hours reduces death or disability in neonates with moderate or severe hypoxic ischemic encephalopathy (HIE) with a number needed to treat (NNT) of 7 (95% CI 5 to 10); and NNT for an additional beneficial outcome in reducing neurodevelopmental disability in survivors of 8 (95% CI 5 to 14) (1, 2, 3, 4, 5). Benefits of HT persist into early childhood with increased proportion of cooled children having IQ >85 (6, 7), and less severe cerebral palsy (8).
HT is typically administered in newborn infants as wholebody cooling (WBC) using different types of mattresses or wraps around the body (3, 4), or as selective head cooling (SHC) using a “coolcap” around the head (2) with water circulating within the “coolcap.” Selective head cooling (SHC) is an excellent technique and Cool-Cap was the first to show neuroprotection by cooling term newborns after moderate or severe perinatal asphyxia. Trends in Protective Hypothermia have moved quickly towards Total Body Hypothermia, and servo controlled units, which is not the case with Cool-Cap which is a non-servo controlled device. The Cool-Cap SHC equipment is currently not supported commercially.
1. To decrease death or disability in the following group of infants
a. ≥35 weeks’ gestation newborn infants <6 hours of age (5)
b. Evidence of asphyxia (at least one of the four criteria below must be met)
(1) Apgar score at 10 minutes of age ≤5
(2) Worst arterial or capillary or venous pH within 60 minutes of life ≤7.0
(3) Arterial or capillary or venous base deficit within 60 minutes of life ≥16 mmol/L
(4) Ventilated or resuscitated for at least the first 10 minutes after birth
AND c OR d AND e
c. Moderate or severe encephalopathy characterized by:
(1) Abnormal consciousness—lethargy or stupor or coma and
(2) Hypotonia or abnormal reflexes (including oculomotor or pupillary abnormalities), or decreased/absent spontaneous activity, or abnormal (distal flexion/complete extension/decerebrate) posture, or absent/weak suck, or incomplete/absent Moro or
d. Clinical seizures and
e. A 30 minutes abnormal background activity or electrical seizures in amplitude-integrated electroencephalogram (aEEG) within the first 6 hours of life
2. If pH is between 7.01 and 7.15 or base deficit between 10 and 15.9 mmol/L or blood gas unavailable and/or aEEG is unavailable or not used as entry criteria, the following criteria can be used (3):
a. ≥35 weeks’ gestation within <6 hours of age and
b. any one of the following
(1) Acute perinatal event such as cord prolapse, uterine rupture, late or variable decelerations
(2) Apgar scores ≤5 at 10 minutes
(3) Prolonged resuscitation: chest compressions and/or intubation and/or mask ventilation at 10 minutes
and
c. Any one of the following
(1) Clinical seizures
(2) Encephalopathy defined as one or more signs in at least three of the following six categories: Level of consciousness, spontaneous activity, posture, tone, primitive reflexes, autonomic system (Fig. 50.1)
B. Special Circumstances
1. Cooling beyond 6 hours of age: In a recent trial (9), 21 centers randomized 168 term infants, who failed the 6-hour time-window, to HT (n = 83) and normothermia (n = 85) over 8 years. Participants had a median (range) postnatal
age of 16 hours (6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24) at the commencement of intervention. Death or disability was comparable between the HT (24.4%) and normothermic group (27.9%) (N-1 Chi squared = 0.25). Experimental studies demonstrate that the therapeutic effect of hypothermia declines linearly up to 9 hours following hypoxic insult and is negligible beyond 9 hours (10, 11). These results indicate that cooling should be commenced before 6 hours of age.
age of 16 hours (6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24) at the commencement of intervention. Death or disability was comparable between the HT (24.4%) and normothermic group (27.9%) (N-1 Chi squared = 0.25). Experimental studies demonstrate that the therapeutic effect of hypothermia declines linearly up to 9 hours following hypoxic insult and is negligible beyond 9 hours (10, 11). These results indicate that cooling should be commenced before 6 hours of age.
 FIGURE 50.1 Clinical pathway for commencing therapeutic hypothermia. (Derived from Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353:1574-1584; Jacobs SE, Morley CJ, Inder TE, et al. Whole-body hypothermia for term and near-term newborns with hypoxic- ischemic encephalopathy: a randomised controlled trial. Arch Pediatr Adolesc Med. 2011;165(8):692-700; Laptook AR, Shankaran S, Tyson JE, et al. Effect of therapeutic hypothermia initiated after 6 hours of age on death or disability among newborns with hypoxic-ischemic encephalopathy: a randomized clinical trial. JAMA. 2017;318(16):1550-1560.; and MedStar Georgetown University Hospital Neonatal Intensive Care Unit.) |
2. Cooling mild HIE: There is currently no published evidence to support using HT for infants with mild HIE (12).
3. Cooling longer (5 days) or deeper (32°C): A four group randomized study found that neither cooling for 5 days or cooling down to 32°C had better outcome than the current protocol of 33.5°C for 3 days. This study was stopped early due to futility (13). Outcome of the 50% who underwent the treatment was recently published confirming the above (14).
C. Contraindications
1. Preterm infants born less than 35 weeks’ gestation due to lack of data regarding the safety and benefit of TH. Hypothermia may be associated with coagulopathy, hypo- or hyperglycemia in preterm infants between 34 and 35 weeks’ gestation with HIE (15).
2. Major congenital anomalies. However, local guidelines might differ. Some centers offer HT to term infants with surgical, cardiac, chromosomal, or sudden unexpected postnatal collapse, who have suffered significant perinatal asphyxial encephalopathy and whose intensive care will be continued (e.g., infant with surgical conditions including ventilated asphyxiated infant with tracheoesophageal fistula requiring imminent surgery) (16, 17), have a cardiac condition (e.g., infant with transposition of great arteries with tight atrial septum leading to HIE), have a chromosomal condition (e.g., infant with trisomy 21 with perinatal asphyxia), and infants suffering postnatal collapse (e.g., sudden unexpected neonatal cardiorespiratory arrest leading to HIE) (17) unless low body temperature might adversely influence the effect(s) of other required treatments (18).
3. Syndromes involving brain dysgenesis, when known.
4. Infants in moribund state.
5. Birth weight below second percentile.
D. Cooling at Birth
1. If the infant fulfills criteria (b) in A by 10 minutes of age, initiate passive HT and core temperature monitoring.
a. Switch off heater in the open warmer/transport incubator.
b. Do not wrap or cover the head with hat (19).
c. Insert rectal or esophageal temperature probe as early as possible.
E. Securing Rectal or Esophageal Temperature Sensor
Rectal Temperature Sensor
1. Measure and mark the rectal temperature sensor (tape bridge) (Fig. 50.2A).
2. Lubricate the first 5 cm before insertion (Fig. 50.2B).
 FIGURE 50.2 Insertion and fixation of rectal temperature sensors. A: Measuring the rectal temperature sensor probe to 6 cm and marking with tape. B: Lubrication of the tip of the temperature sensor. C: Smearing the under surface of the thigh with no-sting barrier film after cleaning the perianal region. D: Sticking a hydrocolloid dressing on the surface of the thigh. (continued) |
3. Insert to 6 cm into the infant’s rectum. Clean the perianal region followed by smearing the under surface of the thigh with a no-sting barrier film (Sorbaderm/Cavilon) (Fig. 50.2C).
4. Stick a hydrocolloid dressing (7 × 3 cm) (duoDERM) on the under surface of both thighs (Fig. 50.2D).
5. Fix the temperature sensor over the hydrocolloid dressing with another (5 × 5 cm) hydrocolloid dressing (Fig. 50.2E).
6. Insert a second rectal probe to 6 cm (Fig. 50.2 E), to be connected to the patient monitor to double check the readings from the rectal probe connected to the cooling machine.
Esophageal Temperature Sensor
1. Insert esophageal probe, preferably via the nostril. If not possible, insert orally. Measure from tip of the nose to ear lobe and to xiphoid then subtract 2 cm
to calculate the length of insertion. This length will position the tip of the sensor 2 cm above the diaphragm.
to calculate the length of insertion. This length will position the tip of the sensor 2 cm above the diaphragm.
 FIGURE 50.2 (Continued) E: Securing two rectal temperature sensors on the side of the thigh. |
2. Obtain a CXR to confirm the position of the tip of the esophageal probe. Attach the esophageal probe to the extension that connects to the cooling machine.
F. Supportive Intensive Care With HT
1. Provide airway support and monitoring: Appropriate respiratory support with ventilator or continuous positive airway pressure, and monitoring of pulse oximetry, pulmonary function, end-tidal CO2, and arterial blood gases.
2. Maintain PCO2 corrected for temperature >35 mm Hg (20) (PCO2 at 33.5°C is approximately PCO2 at 37°C × 0.83). Keep CO2 at normal range of 35 to 50 mm Hg when analyzed at 33.5°C. If analyzed at 37°C, use a range of 42 to 60 mm Hg. Avoid unnecessary exposure to high oxygen concentration (21).
3. Provide cardiac monitoring and support: Arterial blood pressure, cardiac output, and function monitoring (if available). Support cardiac function and perfusion with inotropes and volume as necessary. Heart rate is normally reduced by approximately 10 beats/1°C during HT; however, inotropic support will increase the heart rate (22). Expected heart rate for infants cooled to 33.5°C will be 80 to 100 beats per minute (22).
4. Provide aEEG and EEG monitoring: Use single- or two-channel aEEG recording to assess the background activity, pattern, and monitor the time to normalization of background pattern (23, 24, 25); identify seizures preferably using continuous EEG/aEEG to diagnose subclinical seizures (26), and monitor the effect of anticonvulsants. Some units use multichannel EEG.
5. Actively monitor and treat clinical and electrical seizures, because seizures worsen neurodevelopmental outcome independent of the severity of hypoxic-ischemic brain injury (27). The serum drug levels of anticonvulsants should be monitored closely because of liver impairment in infants with neonatal encephalopathy and potential HT-induced reduction in metabolism (28).
6. Monitor blood glucose from birth and treat hypoglycemia. Hypoglycemia is common in severely asphyxiated infants, particularly within the first 24 hours (29) and is associated with adverse long-term neurodevelopment (30).
7. Monitor serum electrolytes and maintain serum magnesium ≥1 mmol/L, as this may improve the neuroprotection (31).
8. Treat coagulopathy.
9. Sedate the cooled infants with appropriate sedatives to avoid cold stress. Experimental evidence shows that lack of sedation during HT may abolish the neuroprotective effect (32).
10. Monitor urine output. Catheterization may be necessary to maintain accurate fluid balance in sedated cooled infants.
11. Monitor core, surface, and scalp temperature (if on head cooling) every 15 minutes of maintaining HT during rewarming in manual modes. In servo modes, core, surface, and scalp temperatures can be monitored every 30 minutes during maintenance phase of HT.
12. Monitor skin for changes, and change the position of the infant (right lateral, left lateral, supine, and slight tilt of upper body) every 6 hours to avoid pressure sores or fat necrosis from poorly perfused tissue (3) and improve perfusion/ventilation within different areas of the lung.
G. Selective Head Cooling
SHC with mild systemic hypothermia (rectal temperature 34° to 35°C) was the first FDA approved cooling method in clinical use (34) and aims to selectively reduce the temperature of the brain more than the rest of the body, seeking to minimize potential systemic adverse effects of HT (35, 36). It is currently not feasible to accurately measure temperature in different parts of the brain, and the large size of the infant’s head can preclude achieving significant cooling in the deep brain using a cooling cap without reducing core temperature (37). There is no evidence to suggest that either of the cooling methods (SHC or WBC) is superior to the other; however, servo-controlled WBC is easier than SHC and is most commonly used.
In the SHC with mild systemic hypothermia, while the head is cooled using a cooling cap, the body is warmed using an overhead radiant warmer. Advantages of SHC includes
achieving a lower temperature in the cortex and as the body is warm, babies are more comfortable. Disadvantages include lack of servo-control in maintaining the core temperature, which makes the technique labor intensive. SHC with normothermia might be useful to investigate in preterm infants with hypoxic ischemic encephalopathy.
achieving a lower temperature in the cortex and as the body is warm, babies are more comfortable. Disadvantages include lack of servo-control in maintaining the core temperature, which makes the technique labor intensive. SHC with normothermia might be useful to investigate in preterm infants with hypoxic ischemic encephalopathy.
H. Whole-Body Cooling
WBC can be achieved by:
1. Passive cooling.
2. Cooling with simple adjuncts such as water bottles, gloves filled with water, gels, or fan.
These methods are effective, but they are more difficult to use and are labor intensive. It is difficult to achieve stable temperature over a long period.
3. Manually controlled cooling machine and mattress.
4. Servo-controlled cooling machines with body wrap or mattress.
a. Temperature, blood pressure, and heart rate variation during cooling with manual and servo-controlled WBC and manual SHC are shown in Figure 50.3.
 FIGURE 50.3 Variability in the rectal temperature during initiation, maintenance, and rewarming phase of HT. SHC, selective head cooling manual (CoolCap n = 21); WBCmc, whole-body cooling manual control (Tecotherm n = 25); WBCsc, whole-body cooling servo-controlled (CritiCool nv = 28). |
Passive Cooling
After perinatal asphyxia, the metabolism of infants is naturally low, and the core temperature will fall unless active warming is commenced (38). When perinatal asphyxia is likely in an infant at birth, passive cooling should be initiated as soon as ventilation is established (39). This method of cooling can be effective for days, depending on the environmental temperature and frequent control of cooling sources. Passive cooling is usually only used until active cooling equipment is available (40). Passive cooling is used in peripheral centres who do not have servo-controlled cooling machine to commence cooling on babies who fulfil cooling criteria or on asphyxiated babies who have inconclusive neurological examination or mild encephalopathy until the babies could either be assigned to full therapeutic hypothermia protocol or rewarmed.
Technique
1. No radiant warmer or other methods of warming should be initiated.
2. Keep the infant uncovered (small diaper may remain in place).
 FIGURE 50.4 Cooling during transport using Tecotherm (A) or CritiCool mini (B). CritiCool can operate using battery for 1 hour. |
3. Monitor core temperature with rectal or esophageal probe. If overcooling occurs, infant can be rewarmed slowly with a heat source (e.g., warm water bottles, overhead heating [with heat shield to the head]) (see Fig. 50.17).
4. Maintain ambient temperature below 26°C.
I. Cooling During Transport
1. Refer the infant to a center offering therapeutic HT as soon as possible.
2. Provide the required cardiorespiratory support, and use passive or other (see G, I) cooling method to achieve the target temperature early (44) and maintain target temperature using servo control during transport by ambulance (45) or aircraft (Fig. 50.4) (46).
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