Effects of local hypothermia\u2013rewarming on physiology, metabolism and inflammation of acutely injured human spinal cord

Mathew J Gallagher,Leonarda Serdani,Marcel A Kopp,Argyro Zoumprouli,Samira Saadoun,Siobhan Kearney,Marios C Papadopoulos,Oliver Sherwood,Christian Blex,Jan M Schwab,Florence R A Hogg

doi:10.1038/s41598-020-64944-y

Abstract

In five patients with acute, severe thoracic traumatic spinal cord injuries (TSCIs), American spinal injuries association Impairment Scale (AIS) grades A–C, we induced cord hypothermia (33 °C) then rewarming (37 °C). A pressure probe and a microdialysis catheter were placed intradurally at the injury site to monitor intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue metabolism and inflammation. Cord hypothermia–rewarming, applied to awake patients, did not cause discomfort or neurological deterioration. Cooling did not affect cord physiology (ISP, SCPP), but markedly altered cord metabolism (increased glucose, lactate, lactate/pyruvate ratio (LPR), glutamate; decreased glycerol) and markedly reduced cord inflammation (reduced IL1β, IL8, MCP, MIP1α, MIP1β). Compared with pre-cooling baseline, rewarming was associated with significantly worse cord physiology (increased ICP, decreased SCPP), cord metabolism (increased lactate, LPR; decreased glucose, glycerol) and cord inflammation (increased IL1β, IL8, IL4, IL10, MCP, MIP1α). The study was terminated because three patients developed delayed wound infections. At 18-months, two patients improved and three stayed the same. We conclude that, after TSCI, hypothermia is potentially beneficial by reducing cord inflammation, though after rewarming these benefits are lost due to increases in cord swelling, ischemia and inflammation. We thus urge caution when using hypothermia–rewarming therapeutically in TSCI.

Highlights

Hypothermia is being investigated as a potential therapy for traumatic brain injury (TBI)[1] and traumatic spinal cord injury (TSCI)[2] based on compelling evidence from several laboratories and animal species that hypothermia is neuroprotective
We applied our monitoring techniques to define the effect of local hypothermia and rewarming on injury site physiology, metabolism and inflammation in TSCI patients
We previously showed that intraspinal pressure (ISP) measured this way is different from intrathecal pressure measured above or below the injury site because the swollen, injured cord is compressed against the surrounding dura compartmentalising the intrathecal space[18,22,23]

Summary

Introduction

Hypothermia is being investigated as a potential therapy for traumatic brain injury (TBI)[1] and traumatic spinal cord injury (TSCI)[2] based on compelling evidence from several laboratories and animal species that hypothermia is neuroprotective. Despite the encouraging findings of animal studies, randomized controlled human trials have failed to show functional benefit of hypothermia in TBI patients[1,9,10]. Despite the wide interest in therapeutic hypothermia for CNS injuries, there is paucity of mechanistic data from humans regarding the effect of hypothermia on the injury site. In TSCI patients, the effect of cooling and rewarming on cord swelling, metabolism and inflammation are unknown. It is unclear if hypothermia and www.nature.com/scientificreports rewarming have beneficial or adverse effects on the injured human spinal cord. We applied our monitoring techniques to define the effect of local hypothermia and rewarming on injury site physiology, metabolism and inflammation in TSCI patients

Methods

Results

Conclusion