Effects of local hypothermia-rewarming on physiology, metabolism and inflammation of acutely injured human spinal cord

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.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1

Setup. (a) Sagittal T2 pre-operative spinal MRI of the five patients (ISCoPE No. 49, 51, 53, 55, 57). Label shows fractured vertebra. (b) Schematic of setup for monitoring and cooling produced using Canvas Draw 3 for MacOS, https://www.canvasgfx.com/en/products/canvas-draw/. ISP probe and microdialysis catheter lie intradurally, on the surface of the injured cord. Cooling catheter and thermometer are extradural. A heating pad is placed on the skin. (c) Post-operative spinal CT showing ISP probe, microdialysis (MD) and cooling catheters.

Figure 2

Relations between various temperatures. (a) Extradural cool/rewarm regime. (b) Core temperature at target extradural temperatures 33 and 37 °C. (c) Actual extradural temperature at target extradural temperatures 33 and 37 °C. (b,c) Show raw data and mean. Not significant ns, P < 0.0001††.

Figure 3

Effect of cooling-rewarming on ISP, MAP and SCPP. (a) ISP, (b) MAP and (c) SCPP for 12 h before start of cooling (white, Pre), for 12 h at minimum temperature (gray, 33 °C) and for 24 h after the end of rewarming (black, Post). Mean + /− standard error. Not significant, ns; P < 0.0001††.

Figure 4

Effect of cooling-rewarming on injury site metabolites. (a) Glucose, (b) Lactate, (c) Pyruvate, (d) Lactate-to-pyruvate ratio (LPR), (e) Glutamate and (f). Glycerol. Metabolite levels for 12 h before start of cooling (white, Pre), for 12 h at minimum temperature (gray, 33 °C) and for 24 h after the end of rewarming (black, Post). Mean + /− standard error. ns not significant, P < 0.05*, <0.001##, <0.0001††.

Figure 5

Effect of cooling-rewarming on injury site inflammatory mediators. (a) IL1α, (b) IL1β, (c) IL8, (d) IL4, (e) IL10, (f) IP10, (g) MCP1, (h) MIP1α, (i) MIP1β and (j). GROα. Mediator levels for 12 h before start of cooling (white, Pre), for 12 h at minimum temperature (gray, 33 °C) and for 24 h after the end of rewarming (black, Post). Mean + /- standard error. Not significant ns, P < 0.05*, <0.005#, <0.001##.