FIELD OF INVENTION
The invention comprises apparatus and a method for preventing or reducing delayed brain damage in a patient, and headwear for fitting to a patient's head for use with the apparatus and method of the invention.
BACKGROUND OF INVENTION
During brain injury, the brain is deprived of freshly oxygenated blood. Following this, neurons in the brain die soon after or at a later stage occurring hours to days after the insult and are not capable of regeneration. Glial cells, which are non-neuronal cells essential for normal brain functioning, also die. Permanent loss of function is a likely outcome of a severe injury to the brain.
Perinatal hypoxic-ischemic injury continues to be a major cause of death or later neurodevelopmental sequelae. This type of head injury in the neonate occurs during asphyxial, traumatic, toxic, infectious, metabolic, ischemic or hypoxic insults to the brain. Specifically, perinatal asphyxia caused by cord occlusion or associated with intrauterine growth retardation; perinatal asphyxia associated with failure of adequate resuscitation or respiration; near miss drowning, near miss cot death, carbon monoxide poisoning, ammonia or other gaseous intoxication, coma, hypoglycaemia and status epileptics; stroke; cerebral trauma. Experimental and clinical studies have shown that hypoxic ischemic encephalopathy (HIE) is an evolving process. Following the primary phase of energy failure during asphyxia cerebral metabolism may initially recover in a latent phase, but then deteriorate in a secondary phase of brain injury 6 to 15 hours later. In the human infant the severity of delayed energy failure after asphyxia is correlated with adverse neurodevelopmental outcome at one and four years of age.
It appears that hypothermic intervention in pathological processes occurring in the brain after brain injury may result in an improved neural outcome (Marion et al., New Eng. J. Med., 336: 540-546 (1997)). Experimentally, hypothermic treatment following reperfusion after brain injury has been shown to increase numbers of viable neurons (Gunn et al., J. Clin, Invest, 99: 248-256 (1997)).
Hypothermic therapy after brain injury is one method that can be used to rescue neurons and other cells from the phase of delayed brain damage that occurs after reperfusion. It involves cooling the brain tissue to a temperature of 30-34° C. As a consequence, pathological processes leading to delayed neuronal and other cell death are inhibited by as yet unknown mechanism/s.
The adverse consequences of hypothermia and the importance of maintaining newborn infants in the thermoneutral range have been known to pediatricians for the past 40 years, since the classic study by Silverman et al, in which infants 1501 g and more kept in “hypothermic” incubators had temperatures of 34.7±0.7° C. These findings were confirmed in subsequent studies with no cause for this increased mortality found at autopsy. It is thus important to limit the developing whole body cooling associated with cerebral hypothermia
Cooling for hypothermic therapy is presently achieved by cold room technology involving a heat exchanger in heart-lung bypass surgery. This kind of surgery takes place in a room the size of a large commercial freezer. Major drawbacks with the cold room technology include that it is invasive and expensive, as a highly skilled team of medical personnel are necessary to operate a standard heart-lung bypass machine. Cooling can also be achieved by using natural or synthetic icepacks. These kinds of methods and devices have drawbacks. The disadvantages with natural and synthetic icepacks include melting, and the cooling temperature cannot be regulated.
U.S. Pat. No. 5,261,339 discloses a device and method for resuscitating the brain as a result of ischemic and anoxic injuries which comprises a head enveloping helmet and a neck supporting back plate with interconnected hollow cavities through which chilled gas from an activated coolant source or cooled liquids pass to chill the brain and upper spinal column. The device is intended for short-term use in the field at a trauma site on persons who have suffered cardiac arrest, respiratory arrest, stroke, suffocation, drowning or similar, to prevent neurologic injury from immediate lack of bloodflow to the brain, or oxygen to the brain, which may occur within minutes of cessation or substantial reduction of blood or oxygen flow.
SUMMARY OF INVENTION
The invention provides an apparatus and method particularly intended to prevent or reduce the development of delayed brain damage, or the secondary phase of brain damage. It has been found that neuronal rescue may be achieved by cooling the brain for an extended period of hours to days after injury while preferably also warming the general body to maintain and control the body temperature to limit systemic hypothermia.
In broad terms in one aspect the invention comprises apparatus for preventing or reducing the development of delayed brain damage in a patient, comprising:
headwear to be fitted to the patient's head and comprising conduits or passages within the headwear through which a fluid coolant may be circulated to cool the brain;
a reservoir to contain fluid coolant, cooling means to cool and maintain the fluid in the reservoir at a predetermined temperature, piping to connect the reservoir to the headwear, and means to circulate the fluid coolant from the reservoir to the patient headwear; and
warming means arranged to maintain and control the temperature of the rest of the patient's body.
Preferably the coolant comprises a liquid coolant such as water, but other liquids or gases may be used. Preferably a liquid coolant such as water is recirculated back to the reservoir in a closed loop. In an alternative arrangement however, liquid CO2 or similar stored under pressure in a cylinder connected to the headwear may be released so that gaseous CO2 flows within the headwear as a cooling medium before being vented to the ambient environment via an outlet from the headwear.
The warming means may comprise an overhead heater directed to maintain and control the patient's general body temperature against the temperature reducing effect of the cooling of the brain or alternatively a heated mattress on which the patient lies. A heated mattress may comprise fluid conduits or passages through which warm water at a thermostatically controlled temperature is passed, an electrically heated mattress or pad, or a heated jacket which is worn bv the patient or blanket which is placed over the patient. Alternatively again, the warming means may comprise a cradle or cot incorporating heating elements in the walls and/or base of the cradle or cot to create a temperature controlled environment for the patient.
Very preferably the apparatus also comprises a control system arranged to thermostatically control the temperature of both the coolant circulating through the headwear to cool the patient's brain and warming means to maintain the patient's general body temperature, and the temperature differential such that the patient's body temperature is maintained in the range 35-37° C. and typically at 36.5-37° C. and the brain temperature is maintained in the range 30-34° C. and typically in the range 32-34° C.
In broad terms in a second aspect the invention comprises headwear for fitting to a patient's head, comprising a cap or bonnet formed of a soft, pliant material and comprising conduits or passages to circulate a coolant through the headwear to cool the brain.
Preferably the headwear comprises a fabric cap or bonnet comprising a removably fitted plastic cooling pad through which the coolant is arranged to circulate, which may be removed so that the bonnet and cooling pad may be laundered and sterilised separately. The cooling pad may be a lightweight plastic pad formed by heat welding together two plastic layers at selected intervals to create a pad having internal passages through which the coolant can circulate, and an inlet and outlet connection to connect the cooling pad to the fluid supply. It is also possible that the cap or bonnet itself may be formed by heat welding together layers of a synthetic material at selected points to form a cap or bonnet having integral fluid passages.
The outer layer forming the cap or bonnet may have an attractive colour and/or a pattern on its exterior. Alternatively and in one preferred form, the cooling pad is formed by soft plastic tubing woven to form a cooling pad and held together by external ties or similar, which is fitted in the cap or bonnet.
In broad terms in a third aspect the invention comprises a method for preventing or reducing the development of delayed brain damage in a patient, comprising applying headwear to the patient's head and circulating a fluid coolant through conduits or passages in the headwear to cool the brain to a temperature sufficiently below normal body temperature to rescue neurons, thermostatically controlling the coolant temperature to maintain the coolant temperature within a predetermined range for an extended period.
Preferably cooling is maintained for at least 12 hours and more preferably for 24-72 hours post-injury. It is believed that the secondary phase of brain damage may be prevented or minimised even if cooling is not commenced until up to 6 hours post-injury.
Preferably the brain is cooled to a temperature in the range 30-34° C. and most preferably in the range 32-34° C.
Preferably the method also includes warming the patient's general body to maintain general body temperature at about 36.5-37° C. and down to 35° C. if appropriate.
Preferably the method also includes monitoring a patient's brain and body temperatures and controlling the brain cooling and body warming to maintain both the head and body temperatures within predetermined ranges. There is a gradient of increasing temperature from the exterior of the patient's head to the centre of the brain. Brain temperature is preferably assessed and monitored via a nasopharyngeal temperature probe. We have found a nasopharyngeal temperature probe to be a reliable and conveniently used indicator of brain temperature. Brain temperature may be assessed by alternative means such as a temperature sensor in the auditory canal.
With the apparatus and method of the invention, it is believed that neurons and other cells in areas of the brain affected by injury that were destined to die during the period of delayed brain damage will be rescued. The patient recovers with increased chances of survival and decreased or no brain damage. By rescue is meant preventing the death of neurons, glial and other cells that would otherwise die as a consequence of brain injury. Such injury may arise due to asphyxia, ischemia, cardiac surgery, stroke, toxins, infections, trauma, haemorrhage, or surgical damage to the brain for example.
The apparatus and method of the invention are particularly but not exclusively suitable for treating brain injury or potential brain injury in newborn infants. In particular we have found that mild selective head cooling combined with mild systemic hypothermia in term newborn infants following perinatal asphyxia is a safe and convenient method of quickly reducing cerebral temperature, with an increased gradient between the surface of the scalp and the centre of the brain. The safety of mild hypothermia with selective head cooling is in contrast with the historical evidence of adverse effects with greater depths of whole body hypothermia