1 Department of Anaesthesia, Intensive Care and Pain Management, University of Edinburgh, UK. 2 Division of Community Health Sciences (Medical Statistics), University of Edinburgh, UK
* Corresponding author: Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK. E-mail: p.andrews{at}ed.ac.uk
Accepted for publication October 14, 2004.
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Abstract |
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Methods. Air at room temperature and humidity was continuously administered to 15 brain-injured, intubated and mechanically ventilated patients via a sponge-tipped oxygen catheter in each nostril at a combined rate of 115 ml kg1 min1. Brain temperature was measured using a pressuretemperature Camino catheter which is designed to site the thermistor 1 cm into the parenchyma in the frontal lobe. Oesophageal temperature was measured using an oesophageal stethoscope with a thermistor. After establishing baseline for 30 min, patients were randomized to receive airflow or no airflow for 6 h and then crossed over for a further 6 h.
Results. Airflow replicating normal resting minute volume did not produce clinically relevant or statistically significant reductions in brain temperature [0.13 (SD 0.55)°C; 95% CI, 0.430.17°C]. However, we serendipitously found some evidence of selective brain cooling via the skull, but this needs further substantiation.
Conclusions. A flow of humidified air at room temperature through the upper respiratory tracts of intubated brain-injured patients did not produce clinically relevant or statistically significant reductions in brain temperature measured in the frontal lobe.
Keywords: brain, direct brain cooling ; brain, injury ; brain, selective brain cooling ; complications, head injury ; complications, subarachnoid haemorrhage
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Introduction |
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The human brain is believed to have three cooling mechanisms: cooling of venous blood through the entire skin surface, which in turn cools the arterial blood supply to the brain, cooling by heat loss through the skull via the venous sinuses and the diploic and emissary veins, and cooling by heat loss from the upper airways (which is abolished by endotracheal intubation).911 The last two are thought to be mechanisms of selective brain cooling, i.e. ways of reducing brain temperature below that of core trunk temperature.
Mariak and colleagues12 measured the intracranial temperature between the frontal lobes and the cribriform plate in four conscious intubated patients under conditions of mild hyperthermia (oesophageal temperatures ranging from 36.9 to 37.5°C). When airflow through the upper respiratory tract was reinstated by extubation, the brain temperature fell by 0.40.85°C, and in three patients it decreased below the oesophageal temperature.
Methods of cooling the brain that utilize normal physiological mechanisms have not been fully explored clinically. Since intubated brain-injured patients are denied heat loss from the upper airways, our aim was to find out whether restoring airflow, at normal minute volumes, room temperature and humidity, through these patients' noses would produce a decrease in brain temperature and/or selective brain cooling. In this pilot exploratory trial, we were not seeking to determine whether there was a therapeutic effect but to find out whether the method worked.
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Methods |
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The power calculation was based on the data of Mariak and colleagues12 as there are no other data on direct brain temperature measurement with heat loss from the upper airways in humans. With the cross-over design a sample size of 15 patients would give 80% power to detect a treatment effect of 78% of the within-patient standard deviation at the 5% significance level.
From September 2002 to June 2003 we enrolled 15 brain-injured patients admitted to the intensive care unit (ICU) at the Western General Hospital, Edinburgh. All patients were intubated, mechanically ventilated and had intracranial pressure (ICP) monitoring. The level of ICP was considered high and treatments were given when ICP was 25 mm Hg. The cardiovascular parameters monitored were ECG, invasive blood pressure, mean arterial blood pressure (MAP) from arterial line monitor, central venous pressure (CVP) and cardiac output (CO) when indicated. Adequate hydration and nutritional support were provided. Propofol, thiopental or midazolam were used as sedatives. Appropriate analgesia with alfentanil and atracurium as a muscle relaxant were administered if required. Patients with subarachnoid haemorrhage were given nimodipine. Inotropic support (norepinephrine and/or dobutamine) was administered to maintain cerebral perfusion pressure (CPP) above 70 mm Hg and MAP >90 mm Hg.
All intubated ventilated patients with head injury due to trauma or haemorrhage and intracranial pressuretemperature monitoring were screened for inclusion. Thirty-three patients were screened, and 15 of these were recruited. The other 18 could not be studied for the following reasons: not expected to survive (five); fractured base of skull (five); lack of assent (five); other (three). The age of the patients ranged from 17 to 70 yr; six were male, nine were female, nine had traumatic brain injury and six had subarachnoid haemorrhage (Table 1).
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Brain temperature was measured using a pressuretemperature Camino catheter (Integra NeuroCare, Newbury Road, Andover, Hants, UK) designed to site the thermistor 1 cm into the parenchyma in the frontal lobe. The oesophageal temperature was measured with an oesophageal stethoscope (Sims Graseby Ltd, Watford, Herts, UK) with the thermistor sited behind the heart, determined by the position of maximum heart sounds.
Data for most of the physiological parameters were collected electronically at intervals of 1 min. Temperature, interventions and drugs were recorded manually. Microsoft Excel and the Statistical Package for the Social Sciences (SPSS 12.0, SPSS Inc., Chicago, IL, USA) were used for organizing and analysing the data.
The Camino catheter in one patient (patient 13) was replaced during the first (no-airflow) period because the ICP measurements were considered unreliable. Therefore the data from the first Camino catheter was not used in the analysis and hence this patient has no brain temperature and ICP data for the baseline and part of the first (no-airflow) period.
Cleaning of the temperature data was limited to removal of known anomalies in oesophageal temperature. These occurred when boluses of drugs diluted with cold water were administered through the orogastric tube and caused a temporary decrease in oesophageal temperature as the fluid passed the thermistor. No changes in oesophageal temperature occurred when starting and stopping infusions of orogastric feed, because of the rate of administration and because the feed was at room temperature. Objective data validation was possible for the cerebral perfusion pressure (CPP) and the blood pressure.
The median was chosen a priori as a summary descriptor of the minute-by-minute temperature measurements for each individual patient. These medians were then analysed descriptively using parametric methods to derive 95% confidence intervals for mean differences in temperature.
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Results |
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Discussion |
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Figure 1 shows that the median brain temperatures of patients 6, 9, 11, 12 and 15 were variously 0.51.3°C lower in the 6 h with airflow than with no airflow. Patient 15's temperature was on a downward trend during the no-airflow period and this continued through the subsequent airflow period. The other four all had purulent sputum. For example, patient 12 was known to have a Haemophilus influenzae chest infection. Halfway through the airflow period his chest became increasingly productive and he had a rigor; his temperature rose from 38 to 39.4°C and remained above 39°C for almost the entire no-airflow period. Therefore the differences in median brain temperature in these patients are likely to be attributable to an increase in temperature in the no-airflow periods caused by a worsening of their clinical conditions, rather than a reduction in temperature in the airflow periods caused by the airflow.
A change in brain temperature would be expected to occur within 30 min of starting airflow.14 Only patient 10 showed a clinically relevant reduction in brain temperature (0.5°C) after 30 min of airflow. A change due to airflow would be more likely to affect brain temperature alone, or at least affect it to a greater extent than body temperature. However, this patient's oesophageal temperature reduced by the same amount as her brain temperature and therefore the change was more likely to be caused by factors other than the airflow.
The narrow confidence intervals indicate that the negative results of this study were not caused by too small a sample size. Indeed, the study had 80% power to detect a change of 0.44°C in the median brain temperature over the 6 h with airflow (Fig. 1) and a change of 0.12°C after 30 min of airflow. However, there are a number of alternative possible explanations for our inability to demonstrate a reduction in brain temperature.
It is possible that brain cooling by heat loss through the upper airways does not occur in humans, although this seems unlikely since various investigators, notably Mariak and colleagues,12 have demonstrated that it does. There is a view that selective brain cooling only occurs during hyperthermia and not during normothermia or fever.10 It is supposed that selective brain cooling is not necessary in normothermia because the brain can be sufficiently cooled by arterial blood from the trunk.10 However, although they do not point this out, Mariak and colleagues12 demonstrate selective brain cooling in normothermia in humans. Towards the end of their study, the oesophageal temperature in one patient was 36.8°C and in another 37°C; in both cases the brain temperature was about 0.2°C lower. This shows that selective brain cooling can occur in normothermia in humans but that the differential may be smaller. Nevertheless, passively blowing air continuously through the nose may not have the same physiological effect as actively breathing air.
Heat loss from the upper airways may be impaired by severe brain injury because of increased sympathetic tone. Heat loss from the upper airways is reduced, if not abolished, by increased sympathetic tone, which causes nasal mucosal vasoconstriction and hence reduced nasal resistance and reduced heat loss to inspired air.15 16 Sympathetic tone is greatly increased for some days after brain injury,17 and furthermore all but two of our patients were on norepinephrine infusions. It is possible that this affected heat loss from the upper airways with nasal airflow.
The higher the flow rate and the lower the temperature and humidity of inspired air, the more heat it takes up from the body. The patients studied by Mariak and colleagues12 breathed ambient air but were not severely brain injured, having had a minor subarachnoid haemorrhage 710 days previously. When they breathed more intensively this produced a greater decrease in brain temperature than normal breathing. Einer-Jensen and Khorooshi18 flowed oxygen, with no added heat or humidity, through the noses of non-brain-injured intubated rats and showed greater decreases in brain temperature with higher flows. We used air at flow rates commensurate with normal minute volume and at room temperature and humidity, and perhaps this does not result in significant heat loss in the severely brain injured.
If brain cooling by heat loss from the upper airways and heat loss through the skull via emissary veins are complementary mechanisms, it is perhaps more likely that temperature changes due to the first mechanism would be detected nearer to the nasopharynx and changes due to the second nearer to the skull. Tentatively, this may be the case, since Mariak and colleagues12 used two thermocouples, and those sited between the frontal lobes above the cribriform plate recorded a decrease in temperature with extubation whereas those cited subdurally did not. Therefore the position of our brain thermistors may have been too far from the nasopharynx to detect changes due to nasal airflow. However, we did detect temperature changes attributable to heat loss through the skull in one of our patients, although this requires further substantiation.
The thermistor in a Camino catheter is sited approximately 1 cm from the tip and the pressure sensor is at the tip. Towards the end of this study, the manufacturer introduced a red mark to allow the insertion depth of the catheters to be checked externally. Because a good ICP trace was obtained in all the patients studied we are confident that the thermistors were all intracranial. The data from trial patients with catheters that had the insertion depth markers were no different from those of the earlier patients, who had no depth marker. In addition, review of repeat CT scans of some of the patients monitored in the study without the depth marker revealed intraparenchymal placement.
Selective brain cooling is defined as natural cooling of parts of the brain, or the whole brain, below aortic (arterial blood) temperature (Commission for Thermal Physiology of the International Union of Physiological Sciences, 1987). It is probably a moot point what brain means in this context. i.e. is it parenchyma, cerebrospinal fluid, blood or any intracranial temperature. In animal research a reduction in hypothalamic temperature below incoming carotid temperature is generally sought. However, the point about selective brain cooling mechanisms is that they involve heat transfer from inside to outside the cranium (whether through skull or upper airways). Therefore we believe that, in humans, demonstrating reductions in an intracranial temperature potentially due to these heat loss mechanisms is the first step. There is very little human research on heat loss through the upper airways using direct brain temperature measurement. However, the study by Mariak and colleagues12 showed that cooling due to heat loss through the upper airways appears to be local in humans, and the fact that our study did not show a change in frontal lobe temperature with nasal airflow may support this.
It is thought that raised ICP may prevent selective brain cooling because emissary veins are involved in both mechanisms and reversal of emissary flow may not be possible in the presence of raised ICP.14 19 Figure 2 shows the difference in median brain temperature between the airflow and no-airflow periods with median ICP in the airflow period. It suggests that a high median ICP made no difference to our results. In fact the two patients who showed the greatest median decrease in brain temperature with airflow compared with no airflow also had the highest median ICPs in the airflow period. This is not, of course, the same as saying that ICP does not affect brain cooling.
In conclusion, flowing air through the upper respiratory tracts of intubated brain-injured patients, at rates commensurate with normal minute volume and at room temperature and humidity, did not produce clinically relevant or statistically significant reductions in brain temperature measured at a distance from the nasopharynx.
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Acknowledgments |
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References |
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2 Cairns CJ, Andrews PJ. Management of hyperthermia in traumatic brain injury. Curr Opin Crit Care 2002; 8: 10610[CrossRef][Medline]
3 Bernard S, Buist M, Monteiro O, Smith K. Induced hypothermia using large volume, ice-cold intravenous fluid in comatose survivors of out-of-hospital cardiac arrest: a preliminary report. Resuscitation 2003; 56: 913[CrossRef][ISI][Medline]
4 Bernard SA, Gray TW, Buist MD et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002; 346: 55763
5 Hypothermia After Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002; 346: 54956
6 Gadkary CS, Alderson P, Signorini DF. Therapeutic hypothermia for head injury. Cochrane Database of Systematic Reviews 2002; CD001048.
7 Mellergard P, Nordstrom CH. Intracerebral temperature in neurosurgical patients. Neurosurgery 1991; 28: 70913[ISI][Medline]
8 Mellergard P. Changes in human intracerebral temperature in response to different methods of brain cooling. Neurosurgery 1992; 31: 6717[ISI][Medline]
9 Brengelmann GL. Specialized brain cooling in humans? FASEB J 1993; 7: 114852
10 Cabanac M. Selective brain cooling in humans: fancy or fact?. FASEB J 1993; 7: 11436
11 Zenker W, Kubik S. Brain cooling in humansanatomical considerations. Anat Embryol (Berl) 1996; 193: 113[ISI][Medline]
12 Mariak Z, White MD, Lewko J, Lyson T, Piekarski P. Direct cooling of the human brain by heat loss from the upper respiratory tract. J Appl Physiol 1999; 87: 160913
13 Aitkenhead AR and Smith G. Textbook of Anaesthesia, 2nd edn. Edinburgh: Churchill Livingstone, 1999
14 Nagasaka T, Brinnel H, Hales JR, Ogawa T. Selective brain cooling in hyperthermia: the mechanisms and medical implications. Med Hypotheses 1998; 50: 20311[CrossRef][ISI][Medline]
15 Cole P. Upper respiratory airflow. In: Proctor DF, Andersen IB, eds. The Nose: Upper Airway Physiology and the Atmospheric Environment. Oxford: Elsevier Biomedical Press, 1982; 16382
16 Eccles R. Neurological and pharmacological considerations. In: Proctor DF, Andersen IB, eds. The Nose: Upper Airway Physiology and the Atmospheric Environment. Oxford: Elsevier Biomedical Press, 1982; 191214
17 Naredi S, Lambert G, Eden E et al. Increased sympathetic nervous activity in patients with nontraumatic subarachnoid hemorrhage. Stroke 2000; 31: 9016
18 Einer-Jensen N, Khorooshi MH. Cooling of the brain through oxygen flushing of the nasal cavities in intubated rats: an alternative model for treatment of brain injury. Exp Brain Res 2000; 130: 2447[CrossRef][ISI][Medline]
19 Harris BA, Andrews PJD. The rationale for human selective brain cooling. In: Vincent JL, ed. Yearbook of Intensive Care and Emergency Medicine. Berlin: Springer-Verlag, 2002; 73847