Rapid, selective and homogeneous brain cooling with transnasal flow of ambient air for pediatric resuscitation

Abstract

Neurologic outcome from out-of-hospital pediatric cardiac arrest remains poor. Although therapeutic hypothermia has been attempted in this patient population, a beneficial effect has yet to be demonstrated, possibly because of the delay in achieving target temperature. To minimize this delay, we developed a simple technique of transnasal cooling. Air at ambient temperature is passed through standard nasal cannula with an open mouth to produce evaporative cooling of the nasal passages. We evaluated efficacy of brain cooling with different airflows in different size piglets. Brain temperature decreased by 3°C within 25 minutes with nasal airflow rates of 16, 32, and 16 L/min in 1.8-, 4-, and 15-kg piglets, respectively, whereas rectal temperature lagged brain temperature. No substantial spatial temperature gradients were seen along the neuroaxis, suggesting that heat transfer is via blood convection. The evaporative cooling did not reduce nasal turbinate blood flow or sagittal sinus oxygenation. The rapid and selective brain cooling indicates a high humidifying capacity of the nasal turbinates is present early in life. Because of its simplicity, portability, and low cost, transnasal cooling potentially could be deployed in the field for early initiation of brain cooling prior to maintenance with standard surface cooling after pediatric cardiac arrest.

Keywords: Blood flow; high nasal airflow; hypothermia; pediatric; piglet.

Figure 1.

Nasal turbinates increase in complexity with age, resulting in increased surface area and air volume for humidification. (a) Examples of turbinate cross-sections along the nasal axis of a 1.8, 4, and 15-kg piglet and (b, c) Turbinate surface area and air space volume derived from tracing the perimeter of the turbinate and the area within the perimeter summed across consecutive 1-cm cross sections. Values are means ± SD; n = 5 per group.

Figure 2.

At a given airflow, temperature fell at similar rates among 5 brain regions in each age group, indicating no spatial gradient. Temperature was measured in parietal cortex, putamen, thalamus, cerebellum, and olfactory bulb during high nasal airflow of 4 L/min (a, n = 6), 8 L/min (b, n = 6), and 16 L/min (c, n = 6) in 1.8-kg piglets, of 16 L/min (d, n = 6), 32 L/min (e, n = 8), and 48 L/min (f, n = 6) L/min in 4-kg piglets, and 16 L/min (g, n = 7), 32 L/min (h, n = 7), 48 L/min (i, n = 7) in 15-kg piglets. Values are means ± SD; *P < 0.05 between olfactory bulb and other 4 regions, †P < 0.05 between olfactory bulb and cerebellum by repeated measures ANOVA and the Holm-Sidak procedure for multiple comparisons at each time point.

Figure 3.

Dependence of rate of brain cooling on nasal airflow rate. (a) In 1.8-kg piglets, brain temperature (averaged across 5 regions) fell more rapidly by increasing the airflow rate from 4 L/min (n = 6) to 8 L/min (n = 6) and from 8 L/min to 16 L/min (n = 6); *P < 0.05 from 8 L/min, †P < 0.05 from 16 L/min. (b) In 4-kg piglets, brain temperature fell more rapidly with airflow rates of 32 L/min (n = 8) or 48 L/min (n = 6) than with 16 L/min (n = 6); *P < 0.05 from 32 and 48 L/min and (c) In 15-kg piglets, airflow had no differential effect between 16, 32 and 48 L/min (n = 7 per group). Values are means ± SD; data analyzed with two-way ANOVA and Holm-Sidak post hoc comparisons.

Figure 4.

Comparison of brain and rectal temperature. Brain temperature (averaged across 5 regions) fell faster than rectal temperature in 1.8-kg piglets with 16 L/min nasal airflow (c. n = 6), in 4-kg piglets with 32 L/min (e. n = 8) and 48 L/min (f. n = 6) nasal airflow, and in 15-kg piglets with 16 L/min (g. n = 7), 32 L/min (h. n = 7), and 48 L/min (i. n = 7) nasal airflow. Differences between brain and rectal temperature were not significant in 1.8-kg piglets with 4 L/min (a. n = 6) or 8 L/min (b. n = 6) nasal airflow or in 4-kg piglets with 16 L/min (D. n = 6) nasal airflow. *P < 0.05 from rectal temperature at each time point by paired analysis with two-way repeated measures ANOVA and Holm-Sidak post hoc comparisons; Values are means ± SD.

Figure 5.

Dependence of rate of cooling on nasal airflow rate. Box-whisker plots display the duration of nasal airflow at which brain temperature (a) and rectal temperature (b) decreased by 3°C from baseline in 1.8-kg piglets with airflows of 4, 8, or 16 L/min and in 4-kg and 15-kg piglets with airflows of 16, 32, or 48 L/min. *P < 0.05 from 1.8-kg piglets with 4 L/min; †P < 0.05 from 4-kg piglets with 16 L/min airflow by analysis of ranks.

Figure 6.

Mean arterial pressure (Left) and heart rate (Right) in 1.8-kg piglets (a, b), 4-kg-piglets (c, d), and 15-kg piglets (e, f) during the 4-hour cooling period. Brackets show range of times when values differed significantly from baseline by one-way repeated measures ANOVA and the Dunnett’s test for multiple comparison to baseline. Values are means ± SD.

Figure 7.

Turbinate blood flow measured with microspheres did not decrease during evaporative cooling with nasal airflow of 32 L/min. Physiological parameters displayed for 4-kg piglets (Left) and 15-kg piglets (Right) (means ± SD; n = 5) include brain and rectal temperature (a, b), heart rate (c, d), mean arterial pressure (MAP; e, f), turbinate blood flow (g, h), blood flow to the cerebral hemispheres and left cardiac ventricle (i, j), sagittal sinus O₂ saturation and PO₂ (k, l), cerebral oxygen extraction fraction (m, n), and CMRO₂ (o, p). *P < 0.05, **P < 0.01, ***P < 0.001 from baseline by one-way repeated measures ANOVA and the Dunnett’s test for multiple comparison to baseline.