Staircase method for optimized therapeutic hypothermia

1. A method of treating, preventing, reducing the likelihood of having, reducing the severity of and/or slowing the progression of a condition in a subject in need thereof, wherein a body part of the subject has been affected by the condition for a time period T0, comprising:

(a) reperfusing the affected body part for a time period TR;

(b) implementing a first temperature transition C0 by changing a temperature of the subject's body and/or the affected body part to a first target temperature of about 27-33° C., and maintaining the temperature of the subject's body and/or the affected body part at the first target temperature for a time period of T1;

(c) implementing a second temperature transition C1 by changing the temperature of the subject's body and/or the affected body part to a second target temperature, and maintaining the temperature of the subject's body and/or the affected body part at the second target temperature for a time period of T2; and

(d) implementing a third temperature transition C2 by changing the temperature of the subject's body and/or the affected body part to a third target temperature, and maintaining the temperature of the subject's body and/or the affected body part at the third target temperature for a time period of T3,

thereby treating, preventing, reducing the likelihood of having, reducing the severity of and/or slowing the progression of the condition in the subject,

wherein (T1+T2)=xT0+yTR, wherein x and y are integers, or

wherein fT1+(1−f)T2=xT0+yTR, wherein x and y are integers and f is 0-1 or a fraction therebetween.

2. The method of claim 1 , wherein the first target temperature is about 30, 31, 32, or 33° C.

3. The method of claim 1 , wherein C0 is accomplished within about 1-5, 5-10, 10-15, 15-20, 20-25, or 25-30 minutes.

4. The method of claim 1 , wherein the second target temperature is about 34, 35, or 36° C.

5. The method of claim 1 , wherein C1 is accomplished within about 1-5, 5-10, 10-15, 15-20, 20-25, or 25-30 minutes.

6. The method of claim 1 , wherein the third target temperature is about or 38° C.

7. The method of claim 1 , wherein C2 is accomplished within about 1-5, 5-10, 10-15, 15-20, 20-25, or 25-30 minutes.

8. The method of claim 1 , wherein the first target temperature is about 33° C., the second target temperature is about 35° C., and the third target temperature is about 37° C.

9. The method of claim 1 , wherein (T1+T2)=xT0+yTR, wherein x is 1, 2, 3, 4, or 5, and y is 1, 2, 3, 4 or 5.

10. The method of claim 1 , wherein fT1+(1−f)T2=xT0+yTR, wherein x is 1, 2, 3, 4, or 5 and y is 1, 2, 3, 4, or 5 and f is 0, ½, ⅓, ⅔, ¼, ¾, ⅕, ⅖, ⅗, ⅘, ⅙, ⅚, 1/7, 2/7, 3/7, 4/7, 5/7, 6/7, ⅛, ⅜, ⅝, ⅞, 1/9, 2/9, 3/9, 4/9, 5/9, 6/9, 7/9, 8/9, 1/10, 3/10, 7/10, 9/10, or 1.

11. The method of claim 1 , further comprising:

(e) implementing a fourth temperature transition C3 by changing the temperature of the subject's body and/or the affected body part to a fourth target temperature, and maintaining the temperature of the subject's body and/or the affected body part at the fourth target temperature for a time period of T4.

12. The method of claim 11 , further comprising:

(f) implementing a fifth temperature transition C4 by changing the temperature of the subject's body and/or the affected body part to a fifth target temperature, and maintaining the temperature of the subject's body and/or the affected body part at the fifth target temperature for a time period of T5.

13. The method of claim 1 , wherein the condition is hypoxemia, hypoxia, ischemia, myocardial ischemia, cerebral ischemia, cardiac arrest, stroke, ischemic stroke, hemorrhagic stroke, transient ischemic attack, traumatic brain injury, traumatic spinal cord injury, hypoxic-ischemic injury, or hypoxic-ischemic encephalopathy, perinatal asphyxia, or a combination thereof.

14. A system, comprising:

a temperature management module configured for changing and/or maintaining a temperature of a subject's body and/or body part; and

a computer configured for operating the temperature management module to change and/or maintain the temperature of the subject's body and/or body part, wherein the computer comprises

a memory configured for storing one or more programs; and

one and more processors configured for executing the one or more programs, wherein the one or more programs comprise

instructions for operating the system and/or modules thereof to change and/or maintain a temperature of a subject's body and/or body part, and to control the temperature of the subject's body and/or body part in accordance with the method of claim 1 .

15. The system of claim 14 , wherein the temperature management module comprises a cooling catheter, cooling blanket, ice pack, iced lavage, transnasal cooling cannula, cooling helmet, cooling cap, cooling wrap, gel pad, or extracorporeal blood cooling machine, or a combination thereof.

16. A computer, comprising:

a memory configured for storing one or more programs; and

one and more processors configured for executing the one or more programs,

wherein the one or more programs comprise instructions for operating a temperature management module configured to change and/or maintain a temperature of a subject's body and/or body part, and to control the temperature of the subject's body and/or body part in accordance with the method of claim 1 .

17. A computer implemented method of treating, preventing, reducing the likelihood of having, reducing the severity of and/or slowing the progression of a condition in a subject, comprising:

providing the computer of claim 16 ;

connecting the computer to a temperature management module configured for changing and/or maintaining a temperature of a subject's body and/or body part to control the temperature of the subject's body and/or body part, and to detect biomarkers in the subject's body and/or body part; and

operating the computer to operate the temperature management module to change and/or maintain the temperature of the subject's body and/or body part, to control the temperature of the subject's body and/or body part, and to detect biomarkers in the subject's body and/or body part, thereby treating, preventing, reducing the likelihood of having, reducing the severity of and/or slowing the progression of the condition in the subject.

18. A method of treating, preventing, reducing the likelihood of having, reducing the severity of and/or slowing the progression of a condition in a subject, wherein a body part of the subject has been affected by the condition for a time period T0 and then reperfused for a time period TR, comprising:

(a) implementing a first temperature transition C0 by changing a temperature of the subject's body and/or the affected body part to a first target temperature of about 27-33° C., and maintaining the temperature of the subject's body and/or the affected body part at the first target temperature for a time period of T1;

(b) implementing a second temperature transition C1 by changing the temperature of the subject's body and/or the affected body part to a second target temperature, and maintaining the temperature of the subject's body and/or the affected body part at the second target temperature for a time period of T2; and

(c) implementing a third temperature transition C2 by changing the temperature of the subject's body and/or the affected body part to a third target temperature, and maintaining the temperature of the subject's body and/or the affected body part at the third target temperature for a time period of T3,

thereby treating, preventing, reducing the likelihood of having, reducing the severity of and/or slowing the progression of the condition in the subject,

wherein (T1+T2)=xT0+yTR, wherein x and y are integers or

wherein fT1+(1−f)T2=xT0+yTR, wherein x and y are integers and f is 0-1 or a fraction therebetween.