Rapid and selective brain cooling method using vortex tube: A feasibility study
a b s t r a c t
Vortex tubes are simple mechanical devices to produce cold air from a stream of compressed air without any moving parts. The primary focus of the current study is to investigate the feasibility and efficiency of nasopharyn- geal brain cooling method using a vortex tube. Experiments were conducted on 5 juvenile pigs. Nasopharygeal brain cooling was achieved by directing cooled air via a catheter in each nostril into the nasal cavities. A vortex tube was used to generate cold air using various sources of compressed air: (I) hospital medical air outlet (n = 1); (II) medical air cylinders (n = 3); and (III) scuba (diving) cylinders (n = 1). By using compressed air from a hospital medical air outlet at fixed inlet pressure of 50 PSI, maximum brain-rectal temperature gradient of
-2?C was reached about 45-60 minutes by setting the flow rate of 25 L/min and temperature of -7?C at the
cold air outlet. Similarly, by using medical air cylinders at fill-pressure of 2265 PSI and down regulate the inlet pressure to the vortex tube to 50 PSI, brain temperature could be reduced more rapidly by blowing -22?C +- 2?C air at a flow rate of 50 L/min; brain-body temperature gradient of -8?C was obtained about 30 minutes. Fur- thermore, we examined scuba cylinders as a portable source of compressed gas supply to the vortex tube. Like- wise, by setting up the vortex tube to have an inlet pressure of 25 PSI and 50 L/min and -3?C at the cold air outlet, brain temperature decreased 4.5?C within 10-20 min.
(C) 2016
Hypothermia is known to reduce the chances of brain tissue damage when oxygenated Blood supply to the brain is diminished as may occur during ischemic or anoxic events such as cardiac arrest [1,2]. The neuro- protective benefits of hypothermia have been linked to the time to ini- tiate cooling after injury, depth of cooling and re-warming rate [3,4]. The general agreements among clinicians are early cooling initiation within the treatment window after injury, and gradual rewarming (i.e., 0.1?C/h-0.4?C/h) [5,6]. The optimum target temperature for thera- peutic hypothermia is still uncertain. Although some clinical studies in- dicate that the temperature range associated with better outcomes appears to be 32?C to 35?C [7,8], a recent study revealed no significant difference between hypothermic and near-normothermic treatment
? Conflicts of Interest: MFB, LK, and T-YL are inventors on patent application PCT/ CA2015/050,216 submitted on March 4, 2013, describing the Selective brain cooling method.
?? Sources of Funding: Lawson Health Research Institute.
* Corresponding author at: Imaging Research Laboratories, Robarts Research Institute, 1151 Richmond Street, North London, Ontario, N6A 5B7. Tel.: +12 519 639 7897;
fax: +1 519 663 3078.
E-mail address: [email protected] (M. Fazel Bakhsheshi).
1 All work was performed in this institution.
groups (33?C and 36?C) in patients after cardiac arrest in terms of their survival and neurologic outcome [9]. Moreover, cooling the whole body below 34?C can induce severe complications including shiv- ering, skin erythema, renal failure, coagulopathy, pulmonary hyperten- sion and increased mortality [10]. Moreover, it may decrease perfusion and oxygenation by impairing myocardial contractility, reducing cardiac output and making the heart more prone to arrhythmia [11]. Conse- quently, to maximize neuroprotective effects such as preventing inflam- matory cascades in brain yet minimize systemic complications, delivery of selective cerebral hypothermia would be advantageous.
Cooling the nasopharynx may offer the capability to cool the brain selectively due to anatomic proximity of the Internal carotid artery to the cavernous sinus. Furthermore, cerebrospinal fluid chilled at the basal cistern cools the whole brain through the cerebrospinal fluid cir- culation. Vortex tubes, also known as Ranque-Hilsch vortex tubes [12,13], are very simple mechanical devices to produce cold and hot air from a stream of compressed air without any moving parts, which are typically used for commercial Low Temperature applications such as cooling of electrical parts, control units, cutting tools and mechanical, electronic or electrical components under severe thermal stresses [14]. In this report, we have investigated whether spraying cooled air pro- duced by a vortex tube into nasal cavities is an effective and simple cooling method to selectively reduce and maintain brain temperature
http://dx.doi.org/10.1016/j.ajem.2016.02.001
0735-6757/(C) 2016
on normal juvenile pigs. Furthermore, we examined different sources of compressed breathable gas supply to the vortex tube and outputting cooled air from the vortex tube.
supply to the vortex tube [15] (Adjustable cold air gun, ITW Vortec, Ltd)(Fig. 2) were tried:
I. Hospital medical air outlet at fixed outlet pressure of 50 PSI (n =
- Methods and apparatus
1)(method I);
II. Medical air cylinders with the capacity of 232 ft3
at fill-pressure
Animal preparation and experimental procedure
Experiments were conducted on 5 juvenile Duroc pigs with an aver- age age of 2 to 3 weeks and an average weight of 14 kg +- 4 kg. All ani- mal experiments were approved by the Animal Use Subcommittee of the Canadian Council on Animal Care at the University of Western On- tario. Animals were obtained from a local supplier on the morning of the experiment. Piglets were induced with 4% isoflurane and then main- tained on 2% to 3% for preparatory surgery. The 4% isoflurane provided a rapid induction of anesthesia within 15 to 30 seconds, whereas the 2% to 3% isoflurane maintained surgical anesthesia, allowing surgical proce- dures to be performed without any physiological signs of pain or chang- es of hemodynamic parameters. A tracheotomy was performed and the animal was ventilated with a volume-controlled mechanical ventilator to deliver oxygen/medical air mixture (2:1). A femoral artery was cath- eterized to monitor heart rate (HR) and mean arterial blood pressure (MAP) and to intermittently collect arterial blood samples for gas (PaCO2, PaO2), pH and glucose analyses. Arterial CO2 tension (PaCO2) was monitored throughout the experiment, either directly by blood gas or by the end-tidal CO2 tension measurements, and maintained at normocapnia between 37 and 42 mmHg by adjusting the breathing rate and volume. Arterial oxygen tension (PaO2) was maintained at a level between 90 and 130 mmHg by adjusting the ratio of oxygen to medical air. Blood glucose was monitored intermittently and if it fell below 4.5 mmol/L, a 1 and 2 mL infusion of 25% glucose solution was ad- ministered intravenously. Rectal temperature was recorded from a rec- tal probe inserted to 3 to 4 cm from the anal margin. Brain temperature was also measured continuously with a thermocouple probe. A burr hole 1.5 cm posterior to the bregma along the mid-line was made in the skull with a Dremel tool. The needle thermocouple probe was inserted through the burr hole into the brain to a depth of 2 cm from the brain surface to measure brain temperature. After surgery, each pig together with a recirculating heated water blanket were wrapped with linen blankets to keep core temperature at 38.5?C +- 0.5?C and an- esthesia was maintained on 1% to 2% isoflurane.
Method of nasopharyngeal brain cooling
A schematic of a typical vortex tube is shown in Fig. 1. It comprises an air inlet nozzle, a vortex generation chamber, a cold-end orifice, a hot-end control valve and a tube. Compressed air enters through the inlet nozzle. The air passes through a generation chamber which spins the air centrifugally along the inner walls of the tube at a high rate of an- gular velocity (1,000,000 RPM) toward the opposite end of the tube where a control valve allows some of the air to escape. The remaining air is forced back through the center of the incoming air stream to exit as cold air through the cold air outlet next to the compressed air inlet nozzle. The fraction of compressed air exiting as cold air is called the Cold Fraction. The following sources of compressed breathable gas
of 2265 PSI (supplied by L’Air Liquide, Ltd) at variable vortex tube inlet pressure of 10, 25, 35 and 50 PSI (n = 3) (method II);
III. Scuba (diving) cylinders with the capacity of 100 ft3 at fill- pressure of 2640 PSI at vortex tube inlet pressure of 15 and 25 PSI (n = 1) (method III).
A custom-made catheter (made from Polyvinyl Chloride, PVC), coat- ed with 2% Lidocaine gel for anesthesia and better contact with turbinate in the nasal cavity, was inserted 8 to 10 cm into each nostril. The nasal catheter comprises a tubular body defining a lumen and an open end in continuous fluid communication with the cold air outlet of a vortex tube and first and second tubular nasal prongs extend from the tubular body.
In Fig. 3, the schematic of the experimental setup is shown. Nasopharygeal brain cooling was achieved by directing cooled air via a catheter in each nostril into the nasal cavities. The cold air flow rate was set by the fraction control valve of the vortex tube to the desired flow rates of 25 or 50 L/min as measured by a flowmeter (VWR Flowme- ters Acrylic, FR4500 series with accuracy of +-3%, VWR International Inc). The temperature of air at the cold air outlet was monitored and re- corded continuously with a thermometer (VWR digital thermometer with 0.1?C precision, VWR International Inc). A thermistor was also placed inside of one of the two nasal catheters to monitor temperature of cold air inside the nasal cavity throughout the experiments. During each cooling experiment, both brain and rectal temperatures were mea- sured every 5 minutes.
As well, we investigate the efficiency of cooling with nasal catheter versus face mask in one pig. The inlet pressure was set at 25 PSI while the flow rate at the cold air outlet was set to 25 L/min. Baseline brain and rectal temperature were monitored for 45 to 60 minutes until they did not change for more than 0.5?C in 10 minutes, then the brain was cooled down twice first with the nasal catheters and then with a face mask with a rewarming period to baseline brain temperature be- tween the 2 cooling periods.
- Results
Table 1 displays a summary of the measured physiological parame- ters (MAP and HR) in different experiments. All monitored physiologi- cal parameters showed no significant difference during cooling. No significant changes were found with respect to PaO2, PaCO2, tHb, or pH. Arrhythmias were not observed during cooling.
Fig. 4 demonstrates the brain and rectal temperature profile as a function of time in method I, in which the vortex tube was supplied with compressed air from a hospital medical air outlet at fixed inlet pressure of 50 PSI. With the air flow rate of 25 L/min and temperature of -5?C +- 2?C at the cold air outlet, maximum brain-rectal temperature gradient of -2?C was reached about 45-60 minutes after the initiation of cooling. One hour post cooling, both brain and rectal temperatures decreased from 38?C and 37.4?C to 34.3?C and 35.9?C, which
Fig. 1. Schematic diagram of the operation of a vortex tube showing the flow inlet, the cold and hot air streams, and the cold and hot outlets.
Fig. 2. The adjustable cold air gun [15] incorporates a vortex tube to divide high pressure compressed air (1) into two low pressure streams, one hot and one cold by turning the fraction control valve (2) which allows hot air to flow through a muffling sleeve and out the hot air exhaust (3) while the cold airstream (4) is also muffled and discharges through the flexible hose. The swivel magnetic base (5) provides easy mounting and portability.
corresponded to Cooling rates of 3.7?C/h and 1.5?C/h, respectively. Dur- ing the baseline monitoring period before cooling started, rectal and brain temperature relatively remained constant.
By using medical air cylinders (method II), we could down regulate the inlet compressed air pressure to the vortex tube to 10, 25 or 50 PSI which was much lower than the pressure within the medical air cylin- ders at fill-pressure of 2265 PSI. This pressure drop decreased the tem- perature of the inlet air from that in the air cylinder via the Joule- Thomson effect [16]; thus increasing the air cooling efficiency of the vortex tube. At an inlet pressure of 10 PSI and a flow rate of 50 L/min and a temperature of 13?C +- 1?C at the cold air outlet, Fig. 5A shows that the brain-body temperature gradient was reached to -2?C after 30 minutes of cooling and remained unchanged during the rest of
cooling period. Fig. 5A also demonstrates that brain temperature could be reduced more rapidly, brain-body temperature gradient of -3?C and -7?C was obtained about 30 minutes after the initiation of cooling, at the same flow rate of 50 L/min by decreasing temperature at the cold air outlet to - 3?C +- 1?C and - 22?C +- 2?C by increasing the inlet pressure to 25 PSI and 50 PSI, respectively. All of the abovementioned settings for different inlet pressure were applied on the same pig (rewarming periods between the cooling episodes were not shown in Fig. 5A).
Fig. 5B shows the brain temperature versUS time plot of two separate brain cooling episodes using the same inlet pressure of 35 PSI and a flow rate of 50 L/min and a temperature of -13?C +- 3?C at the cold air outlet on the same pig with a rewarming period between the two cooling
Fig. 3. Schematic representation of the cooling circuit used for nasal cooling showing the locations in the circuit where temperature and flow rate are measured.
Physiological parameters measured at different times during SBC with different methods
Method |
Setting |
Baseline |
Cooling |
|||
15 30 |
45 |
60 |
||||
min min |
min |
min |
||||
Method I |
Shown in Fig. 4 MAP |
54 +- 1 |
54 56 |
53 |
58 |
|
(Compressed air supply from hospital medical air outlet at fixed outlet pressure of 50 PSI) |
Flow rate: 25 L/min (mmHg) Temperature at the cold air outlet: -5?C HR (bpm) |
133 +- 2 |
132 136 |
137 |
140 |
|
+- 2?C |
||||||
Method II |
Shown in Fig. 5A [1] MAP |
44 +- 2 |
45 43 |
46 |
45 |
|
(Medical air supply from compressed air cylinder at fill- pressure of 2265 |
Inlet pressure: 10 PSI (mmHg) |
|||||
PSI) |
Flow rate: 50 L/min HR (bpm) |
110 +- 2 |
116 114 |
115 |
112 |
|
Temperature at the cold air outlet: |
||||||
+13?C +- 1?C |
||||||
Shown in Fig. 5A[2] MAP |
53 +- 4 |
53 52 |
53 |
N/A |
||
Inlet pressure: 25 PSI (mmHg) |
||||||
Flow rate: 50 L/min HR (bpm) |
94 +- 4 |
108 105 |
105 |
N/A |
||
Temperature at the cold air outlet: -3?C |
||||||
+- 1?C |
||||||
Shown in Fig. 5A[3] MAP |
56 +- 1 |
45 44 |
N/A |
N/A |
||
Inlet pressure: 50 PSI (mmHg) |
||||||
Flow rate: 50 L/min HR (bpm) |
99 +- 2 |
108 96 |
N/A |
N/A |
||
Temperature at the cold air outlet: |
||||||
-22?C +- 2?C |
||||||
Shown in Fig. 5B MAP |
38 +- 1 |
42 41 |
44 |
43 |
||
Inlet pressure: 35 PSI (mmHg) |
||||||
Flow rate: 50 L/min HR (bpm) |
110 +- 2 |
108 107 |
110 |
108 |
||
Temperature at the cold air outlet: |
||||||
-13?C +- 3?C |
||||||
Method III |
Shown in Fig. 6, Twin Cylinder MAP |
40 +- 1 |
47 44 |
45 |
50 |
|
(Compressed air supply from scuba cylinder at fill- pressure of 2640 PSI) |
Inlet pressure: 20 +- 5 PSI Flow rate: 50 (mmHg) |
|||||
L/min HR (bpm) |
123 +- 2 |
131 123 |
124 |
133 |
||
Temperature at the cold air outlet: +6?C |
||||||
+- 5?C |
||||||
Shown in Fig. 6, Single Cylinder MAP |
44 +- 1 |
47 46 |
N/A |
N/A |
||
Inlet pressure: 50 PSI (mmHg) |
||||||
Flow rate: 50 L/min HR (bpm) |
135 +- 1 |
142 155 |
N/A |
N/A |
||
Temperature at the cold air outlet: +6?C |
||||||
+- 5?C |
||||||
Nasopharyngeal cooling by mask vs nasal catheter |
Shown in Fig. 7A using nasal catheter MAP |
53 +- 3 |
53 55 |
54 |
N/A |
|
Inlet pressure: 25 PSI (mmHg) |
||||||
Flow rate: 25 L/min HR (bpm) |
112 +- 3 |
112 110 |
112 |
N/A |
||
Temperature at the cold air outlet: -7?C |
||||||
+- 2?C |
||||||
Shown in Fig. 7B using mask MAP |
56 +- 1 |
54 57 |
53 |
N/A |
||
Inlet pressure: 25 PSI (mmHg) |
||||||
Flow rate: 25 L/min HR (bpm) |
116 +- 1 |
119 124 |
128 |
N/A |
||
Temperature at the cold air outlet: -7?C |
||||||
+- 2?C |
N/A, not available.
periods. Following 45-60 minutes of baseline, brain temperature de- creased from 39?C to 35.2?C, corresponding to a brain-body tempera- ture gradient of - 3.8?C, within 15 to 20 minutes of the first nasopharyngeal cooling period. Rectal temperature continued to drop till it reached 37.7?C at 40 minutes post cooling. Both brain and rectal temperature profiles were similar to those shown in Fig. 5A ‘2’ demon- strating the reproducibility of the nasopharyngeal brain cooling meth- od. The cold air input to the nasal catheters was stopped after 40 minutes. The temperature of the pig’s brain then gradually increased till it reached the baseline temperature after an hour of rewarming. The vortex tube was set up in the second episode of brain cooling in the same way as the first one. As shown in Fig. 5B, no significant differ- ences in brain and rectal temperature profiles were induced by the rewarming period between the two series of measurements obtained during nasopharyngeal brain cooling.
Fig. 6 displays the nasopharyngeal cooling approach using single or twin scuba diving cylinders; each has a capacity of 100 ft3 at fill- pressure of 2640 PSI (method III). The vortex tube was set up to have an inlet pressure of 25 PSI and 50 L/min and -3?C at the cold air outlet. As before (Fig. 5), the brain temperature decreased to 33.5?C within 10-20 minutes of cooling. At that time the inlet pressure was decreased to 15 PSI and the temperature at the cold air outlet increased to 6?C +-
3?C. These new operating conditions of the vortex tube were able to maintain the brain temperature at ~33.5?C for another 15 minutes (sin- gle cylinder) or 35 minutes (twin cylinders). Brain and rectal tempera- ture decreased from 37.9?C and 38.5?C to 33.9?C and 37.2?C which corresponded to cooling rates of ?4?C/h and ?1.3?C/h, respectively. During the baseline monitoring period, brain and rectal temperatures variations were the same (brain: 0.1?C; rectal: 0.1?C).
Results of comparing nasopharyngeal cooling via catheter or mask shown in Fig. 7, reveal that brain cooling rate was greater, under the same cooling conditions, when nasal catheters were used as compared with the mask (-3?C in 40 minutes vs -1?C in 40 minutes).
- Discussion
As it occurs very often in science and technology, devices and ap- proaches from one field may find profitable applications in a completely unrelated field, this is the case with the vortex tube. The presented study has investigated that blowing cooled air pro- duced by the vortex tube into nasal cavities is an effective method to selectively reduce and maintain brain temperature on normal ju- venile pigs. Vortex tubes produce cold air from a stream of compressed gas without needing moving parts. The source of
Fig. 4. Brain and rectal temperature over time for nasopharyngeal cooling method at a flow rate of 25 L/min and temperature of -5?C +- 2?C at the cold air outlet. The compressed air was supplied from a hospital medical air outlet at fixed inlet pressure of 50 PSI into the vortex tube (Method I) (n = 1).
compressed gas may be an electrical compressor or a tank or combi- nations of that. We examined different sources of compressed breathable gas supply to the vortex tube. By using compressed air from a hospital medical air outlet at fixed inlet pressure of 50 PSI, brain cooling at the rate of 4?C/h was achieved by setting the flow rate of 25 L/min and temperature of - 7?C at the cold air outlet. Sim- ilarly, by using medical air cylinders at fill-pressure of 2265 PSI and down regulate the inlet pressure to the vortex tube to 50 PSI, brain temperature could be reduced more rapidly by blowing - 22?C +- 2?C air at a flow rate of 50 L/min; brain-body temperature gradient of - 8?C was obtained about 30 minutes after the initiation of cooling. Furthermore, we examined scuba cylinder as a portable source of compressed gas supply to the vortex tube. Likewise, brain temperature decreased from 38?C to 33.5?C within 10-20 minutes of cooling. A thermistor was placed at the tip of one of the two nasal catheters to measure temperature inside the nasal cavity throughout the experiments. Even at a flow rate of 50 L/min and a temperature of - 3?C air was warmed rapidly along the nasal cathe- ters before reaching the nasopharyngeal tissue. An average temper- ature of about 8?C +- 2?C was raised consistently measured with the catheter tip thermistor.
There are some limitations/concerns with our approach that need to be addressed prior to clinical situations. First; there are several anatom- ical differences between pigs and humans (eg, cerebral blood flow, dis- tance from the nasopharynx to the brain, size of the brain, and the area in which heat exchange is carried out). Pigs possess a carotid rete which is surrounded by the cavernous sinus; together these serve as an effec- tive heat exchanger for the brain. Second, the infusion rate and temper- ature at which brain cooling was achieved may be different in humans.
Third, in all of the experimental studies, anesthesia was maintained with 1% to 2% isoflurane, as its administration is easy to apply and quick to control the level of anesthesia. This avoids problems associated with injectable anesthetics, such as a lack of agents to reverse their ac- tivity rapidly in case of overdose or possible side-effects. Isoflurane has been shown to influence systemic arterial blood pressure and cardi- ac output only to a minimal degree over several hours’ induction [17]. Forth, the brain temperature was measured only at one position and therefore, no information was delivered about homogeneity of regional brain temperature. However, two preliminary experiments had exam- ined the temperature gradient within a pig’s brain, calculated as the dif- ference between frontal and parietal lobes by inserting one probe in each region, and this was found to be no more than 0.1?C. A final con- cern with this study is that core body temperature was measured by the rectal temperature which may correlate less well with core temper- ature than esophageal temperature. However, the temperature differ- ence between rectal and esophageal was examined in one experiment and was not more than 0.3?C.
In future studies, the ability of the proposed approach to maintain the target temperature over extended period of time should be ex- plored. As well, more experimental studies are necessary to evaluate the efficiency of the device and reproducibility of the results in different animal models of normal and injured brain. In addition, patient safety is a critical aspect of the evaluation. Although it is unlikely that air at sub- zero temperature and high flow rate will induce freezing damage to the mucosa and embedded blood vessels and nerves of the nasal cavity, his- tological analyses of the excised tissue from the nasal cavities of animals studied should be performed to assess for tissue damages. Moreover, In future studies, we will be examining the nasal cavities to assess for
Fig. 5. Brain and rectal temperature over time for nasopharyngeal cooling method at a flow rate of 50 L/min and temperature of (A) 13?C +- 1?C, -3?C +- 1?C, -22?C +- 2?C and (B) -13?C +- 3?C at the cold air outlet. The compressed air was supplied from medical air cylinders (Method II) at variable inlet pressure of (A) 10, 25 and 50 PSI (all three conditions were applied on the same pig, n = 1) (B) 35 PSI (n = 1).
tissue damage, nasal or nasopharynx mucosal swelling, necrosis or hemorrhage using magnetic resonance imaging. One important aspect which was not tested in our experiments is controlling the Rewarming rate. Rewarming is a critical phase of therapeutic hypothermia in that too fast a rewarming rate may re-trigger destructive processes at the cellular level [18]. Thus, understanding, predicting, and managing pos- sible adverse effects of rewarming are important for guaranteeing hy- pothermia efficacy. To better control cooling and rewarming rates, further development required include developing and testing a proto- type device with a computer-controlled feedback system to automati- cally adjust settings of cold air temperature and flow rate to arrive at desired brain temperature during cooling, maintenance and rewarming phases. Hypothermia may induce metabolic disturbances and electro- lyte abnormalities [19]. Such Electrolyte disorders can lead to the poten- tially Lethal arrhythmias and other harmful complications [20]. Therefore, in the next set of experiments, frequent measurement of electrolytes dur- ing hypothermia will be instituted to prevent critically change in electro- lytes levels and guide the appropriate amount of replenishment. The only disadvantage experienced with the use of the vortex tube during experi- ments was the continuous noise of escaping air, which can be minimized by installing all components in a mobile enclosed cart, which is commer- cially available. No device-related adverse events were observed. No inci- dences of catheter thrombosis, Acute infection, or other complications associated with the insertion procedure were observed.
The successful use of the vortex tube has demonstrated experimen- tally to show selective lowering of brain temperature using various
sources of compressed air as the source of compressed breathable gas and a nasal catheter or a mask as the interface for delivering cooled gas. We have demonstrated that using the vortex tube allows initial rapid and selective brain cooling. This study was the first step in devel- oping a reliable, and efficient cooling device for future clinical trials to ameliorate brain damage from Traumatic brain injuries in children and adults, resuscitated cardiac arrest patients and in stroke patients. Fur- thermore, it should be outlined that the cooling system is inexpensive and reusable which may also be an important argument for a wide spread use of this device. This method can be easily deployed inside and outside of hospital environments as it only requires compressed air to operate.
Author Contributions
Conception and design: all authors. Acquisition of data: M. Fazel Bakhsheshi. Analysis and interpretation of data: M. Fazel Bakhsheshi and L. Keenliside. Drafting the article: M. Fazel Bakhsheshi. Critically revising the article: T-Y Lee. Reviewed submitted version of manuscript: all authors. Approved the final version of the manu- script on behalf of all authors: M. Fazel Bakhsheshi. Study supervi- sion: T-Y Lee.
Acknowledgements
The authors would like to thank Laura Morrison, Lise Desjardins and Jennifer Hadway for their help in conducting the Animal experiments. Also, very special thanks to Terry Kovacevic who provided us scuba div- ing cylinders and technical support.
Fig. 6. Brain and rectal temperature over time for nasopharyngeal cooling method at a flow rate of 50 L/min with an average air temperature of 6?C +- 5?C at the cold air outlet throughout the experiment. The compressed air was supplied from scuba diving cylinders (Method III) at inlet pressure of 25 and 15 PSI (n = 1).
- Quinn MW, Munyard PF. Treatment of asphyxiated newborns with moderate hypo- thermia in routine clinical practice: how cooling is managed in the UK outside a clin- ical trial. Arch Dis Child Fetal Neonatal Ed 2010;95:F152.
- Uray T, Haugk M, Sterz F, Arrich J, Richling N, Janata A, et al. Surface cooling for rapid induction of Mild hypothermia after cardiac arrest: design determines efficacy. Acad Emerg Med 2010;17:360-7.
- Moore EM, Nichol AD, Bernard SA, Bellomo R. Therapeutic hypothermia: benefits, mechanisms and potential clinical applications in neurological, cardiac and kidney injury. Injury 2011;42:843-54.
- Povlishock JT, Wei EP. Posthypothermic rewarming considerations following trau- matic brain injury. J Neurotrauma 2009;26:333-40.
- Jia X, Koenig MA, Shin HC, Zhen G, Pardo CA, Hanley DF, et al. Improving neurolog- ical outcomes post-cardiac arrest in a rat model: immediate hypothermia and quan- titative EEG monitoring. Resuscitation 2008;76:431-42.
- Polderman KH. Mechanisms of action, physiological effects, and complications of hy- pothermia. Crit Care Med 2009;37:S186-202.
- Guidelines for the management of severe traumatic brain injuryJ Neurotrauma 2007;24(Suppl. 1):S1-106.
- Mathur NB, Krishnamurthy S, Mishra TK. Evaluation of who classification of hypother- mia in sick extramural neonates as predictor of fatality. J Trop Pediatr 2005;51:341-5.
- Nielsen N, Wetterslev J, Friberg H. Targeted temperature management after cardiac arrest. N Engl J Med 2014;370:1360.
- Culic S. cold injury syndrome and neurodevelopmental changes in survivors. Arch Med Res 2005;36:532-8.
- Dudgeon DL, Randall PA, Hill RB, McAfee JG. Mild hypothermia: its effect on car- diac output and regional perfusion in the neonatal piglet. J Pediatr Surg 1980;15: 805-10.
- Ranque G. Expe’riences sur la de’tente giratoire avec productions simultane’es d’ume’chappement d’air chaud et d’um e’chappement d’air froid. J Phys Radium 1933;4:112-5 [United States Patent No. 1,952,281 (1934)].
- Hilsch R. The use of the expansion of gases in a centrifugal field as a cooling process. Rev Sci Instrum 1947;18:108-13.
- Eiamsa-ard S, Promvonge P. Review of Ranque-Hilsch effects in vortex tubes. Renew Sustain Energy Rev 2008;12:1822-42.
- Adjustable cold air guns. http://www.Vortec.Nl/our-products/cold-air-guns/.
- Roy B. Fundamentals of classical and statistical thermodynamics; 2002.
- Szczesny G, Veihelmann A, Massberg S, Nolte D, Messmer K. Long-term anaesthesia using inhalatory isoflurane in different strains of mice-the haemodynamic effects. Lab Anim 2004;38:64-9.
- Polderman KH. Application of therapeutic hypothermia in the intensive care unit. Opportunities and pitfalls of a promising Treatment modality-part 2: practical as- pects and side effects. Intensive Care Med 2004;30:757-69.
- Polderman KH, Peerdeman SM, Girbes AR. Hypophosphatemia and hypomagnese- mia induced by cooling in patients with severe head injury. J Neurosurg 2001;94: 697-705.
- Koht A, Cane R, Cerullo LJ. serum potassium levels during prolonged hypothermia. Intensive Care Med 1983;9:275-7.
Fig. 7. Changes in the brain-rectal temperature over time by setting the cold air flow rate from the vortex tube to 25 L/min for nasopharyngeal cooling using (A) nasal catheters and (B) the face mask. The average air temperature at cold air outlet was -7?C +- 2?C. The compressed air was supplied to the vortex tube at an inlet pressure of 25 PSI from a medical air tank (n = 1).