Hypothermia and cerebrovascular reactivity
Utrecht, The Netherlands
* E-mail: o.l.cremer{at}umcutrecht.nl
Editor—Lavinio and colleagues1 have touched upon an important topic by suggesting that temperatures above 37°C may cause hyperaemic derangement of cerebrovascular reactivity in severely head-injured patients. However, one of the major limitations of their retrospective analysis lies in the fact that the effects of temperature could not be separated from any temporal changes that occurred in the brain after injury. Rewarming took place at a time when inflammatory responses in the brain presumably had evolved significantly compared with when the patients were cooled.2 Indeed, the authors acknowledge that the fever and loss of autoregulation observed in their patients may both, in fact, be epiphenomena of inflammation and suggest that prospective studies be performed. In this respect, I would like to draw attention to a study that may provide some additional insight into this matter.
In 2004, we reported on the use of systemic hyperthermia as an experimental therapy for patients with chronic hepatitis C virus infection, who are non-responders to conventional treatment with interferon.3 During 23 experiments at 41.8°C, we continuously measured cerebral oxygen extraction and middle cerebral artery blood flow velocity in patients. At regular temperature intervals, we formally assessed cerebral pressure-flow autoregulation by static tests using phenylephrine infusion, and by measuring the transient hyperaemic response to carotid compression and release. Our data showed that temperatures exceeding 40°C were associated with a marked decrease in cerebral oxygen extraction, a proportional increase in cerebral blood flow velocity, and a transient impairment of pressure-flow autoregulation. These associations remained after multivariate adjustment for variations in arterial partial pressure of carbon dioxide, mean arterial pressure, and propofol blood concentration.
The current findings by Lavinio and colleagues1 seem to confirm these earlier observations of transient cerebral vasoparalysis and hyperaemia during profound hyperthermia in patients with normal brains. However, their data suggest that similar effects become apparent at much lower temperatures in patients with head trauma, possibly reflecting an increased vulnerability of the injured brain to the deleterious effects of heat.
Cambridge, UK Brescia, Italy
* E-mail: andrea.lavinio{at}gmail.com
Editor—We thank Dr Cremer for his comments. Cremer and colleagues3 previously demonstrated that systemic temperature exceeding 40°C is associated with partial vasoparalysis of cerebral vessels in normal brains. Our findings suggest that a similar scenario may happen in head-injured patients exposed to moderate hypothermia for refractory intracranial hypertension.1
Cremer highlights that in our series of brain-injured patients, the hyperaemic derangement of cerebrovascular reactivity became apparent as soon as rewarming from moderate hypothermia exceeded the 37°C brain temperature threshold, reflecting a significantly increased vulnerability of cerebrovascular reactivity of the injured brain. We also emphasize that this phenomenon is commonly undetected by plain intracranial pressure (ICP) monitoring, which lacks explicit information about cerebral vasoreactivity. In this regard, a steady ICP after rewarming from moderate hypothermia is often falsely reassuring, inducing suboptimal control of systemic temperature in brain-injured patients.
To provide further insight into this topic, we would like to share our unpublished observations regarding a series of 15 patients with head injury, matched for age and severity of injury to the study population1 but never exposed to brain temperatures lower than 35°C. Although the cerebral pressure reactivity index (PRx) was demonstrated to be linearly related to brain temperature in the temperature range of 37–39°C in patients treated with moderate hypothermia (R = 0.53; n = 17, P = 0.03), in this second group of patients, we did not observed any significant relationship between brain temperature and PRx (n = 15, P = 0.83). It must be noted that average PbCO2 was similar in the two groups [PbCO2 mean difference = 2 mm Hg (0.21 kPa); P = 0.36]. Similarly, PbO2 in patients treated with moderate hypothermia [PbO2 = 17 (10) mm Hg; 2.3 (1.4) kPa] was comparable with PbO2 in the group of patients not exposed to hypothermia [PbO2 = 20 (11) mm Hg; 2.6 (1.5) kPa, P = 0.45]. However, although average PRx significantly correlated with PbO2 in patients exposed to moderate hypothermia (R = 0.66; n = 17, P = 0.004), in the same temperature range there was no significant relationship between PRx and PbO2 in the group of patients who were not actively cooled (n = 15, P = 0.78). We also investigated the relationship between PRx and brain temperature within all individual patients. In patients exposed to hypothermia, PRx and brain temperature are positively correlated in 16 (67%) of 24 cases [median R = 0.85; IQR (0.80–0.88)], whereas in controls a positive correlation between PRx and brain temperature was observed only in four (26%) out of 15 patients [median R = 0.00; IQR (–0.88 to –0.87); P < 0.01). In summary, temperature-dependent hyperaemic derangement of cerebrovascular reactivity seems to be a phenomenon specifically related to therapeutic hypothermia for refractory intracranial hypertension. However, it must also be emphasized that none of our patients was exposed to temperatures exceeding 40°C. Therefore, our findings do not contradict Cremer's experimental observations.
In conclusion, the exposure to moderate hypothermia seems to play an independent role in determining the vulnerability of cerebral vessels to rewarming in brain-injured patients.
References
1 Lavinio A, Timofeev I, Nortje J, et al. Cerebrovascular reactivity during hypothermia and rewarming. Br J Anaesth (2007) 99:237–44.
2 Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth (2007) 99:4–9.
3 Cremer OL, Diephuis JC, van Soest H, et al. Cerebral oxygen extraction and autoregulation during extracorporeal whole body hyperthermia in humans. Anesthesiology (2004) 100:1101–7.[CrossRef][Web of Science][Medline]
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