Method and composition for resuscitation

Abstract

The key obstacle for current resuscitation is the acutely limited time window. The major reason for the limited time window is that the brain is extremely vulnerable to hypoxic-ischemic insult. The existence of cerebrospinal fluid (CSF) is the major reason why brain and spinal cord is so vulnerable. A method and a composition for resuscitation of cardiac arrest are provided. The method includes steps of inhibiting CSF production, removing CSF or replacing the CSF with invented composition plus conventional CPR. The composition includes colloidal osmotic agent, insulin, elevated magnesium concentration and ATP in artificial CSF.

Description

BACKGROUND OF THE INVENTION [0001] 1. Field of the Invention [0002] This invention is related to a method and a medical composition for resuscitation. In particular, the invention relates to protection of the brain and spinal cord during resuscitation of cardiac arrest. This patent is a continuation of my previous patient application. [0003] 2. Background Information [0004] It is estimated that more than 350,000 Americans died of sudden cardiac arrest each year, more than 95 percent of victims die before reaching the hospital. Economic costs for trauma related arrest is over 400 billion dollars each year. Despite numerous scientific advances throughout modern medicine, outcome of resuscitation for arrest victims remains poor, and outcomes in trauma related battlefield statistics have not improved significantly since the Civil War. The cardiopulmonary resuscitation (CPR) practice including ventilation, closed chest compressions or cardiac massage and defibrillation (step ABC, i.e. Ai...

AI Technical Summary

Benefits of technology

[0018] Although the existence of the CSF causes vulnerability of the CNS, it also provides an opportunity for treatment. Completely removing the CSF, or replacing the CSF with modified CSF (increasing the COP, Mg2+, ATP, and insulin concentration) will reduce the cerebral edema herein increasing the cerebral blood flow and protecting the brain and spinal cord tissue. Mild acidosis environment in CSF will enhance glycolytic capacity increasing the tolerant ability of cerebral tissue to ischemic injury.

[0020] I have found removing the CSF from subarachnoid spaces can effectively prolong the time window for conventional CPR procedure. I have found that replacing the CSF with the invented composition also can effectively prolong the time window for conventional CPR procedure. To use the method to rescue a cardiac arrest patient, first injecting Furosemide or Acetazolamide to stop CSF production, then the CSF will be removed completely from subarachnoid spaces as early as possible, it is preferable that the removal of the CSF start even before conventional CPR. The CSF removal eliminates the major source of water causing cerebral edema, and prevents the onset of the “no-reflow” phenomenon or “hypoperfusion”, making CNS tissue resistant to ischemia, and lengthening the therapeutic window for resuscitation. This method is especially suitable for out-of-hospital application before the patient can be transferred to a medical center. The CSF drainage was first used to prevent spinal cord damage during thoracic aorta surgery in 1957 by a group of Japanese surgeons (Miyamoto K, et al, J cardiovasc surg. 1960; 16: 188-197). More than 45 years of experiences have proven that CSF drainage is the most effective way to prevent paraplegia in majority of the cases. However, some medical centers also reported failure to prevent paraplegia by CSF drainage (Crawford E S et al, J Vasc Surg. 1991; 13(1): 36-46). I have proven that the CSF is so toxic that a small amount of CSF left in subarachnoid space can damage the local tissue and significantly influence the outcome (I believe the failures reported by Crawford ES et al are simply because of controlling the ICP below the central venous pressure, such pressure control leave large amount of CSF around ischemia damaged spinal cord region). Therefore we must understand that although the CSF removal alone is effective to prolong the time widow for resuscitation, it might not be able to reach the maximum protection. The contour of the CNS is very complex with many sulci, and gyri, therefore complete removal of CSF might be a little bit challenging. Therefore, simple CSF removal might inevitably leave part of the tissue unprotected, this can lead to localized tissue damages despite of successful general resuscitation. Therefore I have invented a composition to replace the CSF. The composition is particularly useful for replacing the CSF that can not be removed from subarachnoid space. To use the composition, after CSF removal, the composition will be injected into subarachnoid space to replace the CSF. The composition can be administered through one infusing catheter and one draining catheter positioned in subarachnoid spaces. The high concentration albumin or gelatin increases COP of the composition limiting “free flow” water. The presence of insulin, ATP, the elevated Mg2+ concentration and the mild acidosis in the composition increase glycolytic capacity, yield more energy to ischemia challenged brain. Elimination of cerebral edema prevents the onset of the “no-reflow” phenomenon or “hypoperfusion”, making CNS tissue resistant to ischemia, and lengthening the therapeutic window for resuscitation.

[0022] 1. Removing the CSF has been used to prevent paraplegia during aortic cross-clamping. Furosemide or Acetazolamide has been used in clinic for many years. Therefore, injecting Furosemide or Acetazolamide followed by removing the CSF in addition to conventional CPR can be easily adopted in clinic as a new resuscitation protocol to rescue cardiac arrest. This simple approach can effectively prolong the time window for resuscitation.

Problems solved by technology

However, CPR procedures lack an important step of protecting brain, therefore the time window for resuscitation is the acutely limited.

In clinic, the real problem in resuscitating a patient with circulatory arrest is usually not to restore cardio-pulmonary function but instead to prevent “brain death”.

The CNS tissue including brain and spinal cord is very vulnerable to hypoxia-ischemia, the reason for this has not been clear, and no effective approaches has been available to protect brain and spinal cord.

The CSF is very prone to edema because it lacks macromolecules due to the brain-CSF barrier.

Cardiac arrest results in complete cerebral ischemia, this leads rapid development of cerebral edema.

While excessive Na+ and water molecules inside the cell body is toxic, swelling of the cerebral tissue makes the Virchow-Robin space smaller and may even cause it to collapse, thereby compressing the small blood vessels and resulting in obstruction of the blood flow, such as a “hypoperfusion” or even “no-reflow” phenomenon, which prolongs the original ischemic duration, blocks collateral circulation and induces a feedback loop.

These cascade events result in irreversible cell death, tissue necrosis and liquefac-events result in irreversible cell death, tissue necrosis and liquefaction, finally leading to brain death.