Determinants of effective cooling during endovascular hypothermia

Abstract

Background: Therapeutic hypothermia is a promising neuroprotective therapy with multiple mechanisms of action. We demonstrated the feasibility of thrombolysis combined with endovascular hypothermia, but not all patients achieved effective cooling. We sought to identify the factors that determined effective cooling.

Methods: In 26 patients who underwent endovascular hypothermia, we computed four measures of effective cooling: time to reach target; Area-Under-the-Curve (AUC) 34 ratio; AUC-34; and AUC-35. By multivariate regression, we examined the effects of age, weight, starting temperature, body mass index, body surface area (BSA), gender, shivering, and total meperidine dose on the four outcome measures.

Results: In univariate analyses, all four outcome measures were significantly influenced by BSA (p < 0.01 in all univariate analyses). Time to reach target temperature was quicker in older patients (p < 0.01). Shivering and meperidine dose were highly intercorrelated (r = 0.6, p < 0.01) and both marginally influenced all four outcome measures. In multivariate analysis, AUC ratio and time to reach target temperature were significantly influenced by BSA (p < 0.01) and meperidine (p < 0.05); AUC-34 was influenced only by BSA (p < 0.01). The AUC-35 was influenced by BSA (p < 0.01), shivering, and total meperidine dose (p < 0.05).

Conclusions: The most important determinant of effective cooling during endovascular hypothermia is BSA; larger patients are more difficult to cool and maintain in therapeutic range. Older patients cool more quickly. Shivering was well controlled by the combination of meperidine, buspirone, and surface counter-warming and only minimally influenced cooling effectiveness. Future trials of therapeutic hypothermia may include added measures to cool larger patients more effectively.

Figures

Figure One

Time to Target Temperature. Histogram of the times to reach target temperature for 26 patients treated with endovascular hypothermia. Temperatures were not recorded before 20 to 30 minutes (depending on the starting temperature) so the fastest recorded time is 20 minutes. For each patient shown, the upper temperature is the lowest temperature achieved during the 24-hour cooling period; the lower temperature is the first temperature recorded below 34°C or if no such temperature was recorded, the lowest temperature achieved. The weight of each patient (kg) appears along the x-axis. Patients shown with a black bar received the standard 10.7 F catheter; the grey bars represent the larger 14 F catheter. (Adapted with permission from Hemmen et al, 2009).

Figure Two

A: Representative cooling curve for a patient who cooled quickly. The method for calculating the AUC is described in the text. This patient cooled quickly; the first temperature taken (at 99 minutes after cooling) was below the target temperature of 34°C. B: Representative cooling curve for a patient who never achieved the target temperature. C: Representative cooling curve for a patient who cooled to below target but could not be maintained below the target temperature.

Figure Two

A: Representative cooling curve for a patient who cooled quickly. The method for calculating the AUC is described in the text. This patient cooled quickly; the first temperature taken (at 99 minutes after cooling) was below the target temperature of 34°C. B: Representative cooling curve for a patient who never achieved the target temperature. C: Representative cooling curve for a patient who cooled to below target but could not be maintained below the target temperature.

Figure Two

A: Representative cooling curve for a patient who cooled quickly. The method for calculating the AUC is described in the text. This patient cooled quickly; the first temperature taken (at 99 minutes after cooling) was below the target temperature of 34°C. B: Representative cooling curve for a patient who never achieved the target temperature. C: Representative cooling curve for a patient who cooled to below target but could not be maintained below the target temperature.