Thermoregulation and neuroanesthesia.

Thermoregulation is the mechanism by which body temperature, mainly regulated by hypothalamus, remains stable at 37°C. Afferent pathways reach this brain structure from cutaneous thermal receptors and thoracic-abdominal viscera through the spinothalamic tract and the trigeminal nerve. Under physiological conditions, small variations in body temperature between 0.2°C and 0.4°C trigger efferent compensatory responses. Apart from voluntary behavior changes, responses to cold are: vasoconstriction of arterio-venous shunts of hands and feet, and shivering- and non-shivering–producing thermogenesis (infants <1 year). The responses to heat include precapillary vasodilatation and sweating. Autonomic nervous system plays an essential role in the thermoregulatory response, unique to the patient under general anesthesia.[1]

Thermoregulatory response thresholds are subject to physiological variations (gender, age, circadian changes, exercise), but can also be modified in pathological situations (fever, obesity, hypo- or hyper-thyroidism, hypothalamic–pituitary abnormalities, dysautonomia) or by the action of some drugs.[2]

The effect of anesthetic drugs on the thermoregulatory response has been previously described.[34] Except for midazolam, with minimal effects, anesthetic drugs (fentanyl, alfentanil, sufentanil, propofol, halothane, isoflurane, desflurane, sevoflurane, and nitrous oxide) inhibit, in a dose-dependent way, the thermoregulatory response. In general, a slight increase in the response threshold to heat (sweating) and a strong decrease in the thermoregulatory response threshold to cold (vasoconstriction and shivering) take place. This decrease in the vasoconstriction and shivering threshold is linear for propofol and nonlinear for halogenated agents. The overall result is that general anesthesia increases up to 20 times (from 0.2–4°C) the thermoregulatory response inter-threshold range. So, within this temperature range, the surgical patient is unable to regulate his/her body temperature regardless of ambient temperature (poikilothermia).

Other drugs commonly used in anesthesia also alter the thermoregulatory response. Ketamine reduces the magnitude of redistribution hypothermia, maintaining vasoconstriction of arterio-venous shunts during induction of anesthesia.[5] Muscle relaxants inhibit the tremor, and therefore accentuate hypothermia.[6] Meperidine has a powerful anti-tremor effect, decreasing the shivering threshold twice as much as the vasoconstrictor response.[7] Dobutamine accentuates hypothermia because it enhances cardiac output and increases the convective heat transfer from central to peripheral compartment.[8] Anti-cholinergic drugs increase the threshold for sweating, promoting hyperthermia.[9] Phenylephrine reduces heat loss redistribution due to precapillary vasoconstrictor effect and its negative inotropic effect.[10] Ephedrine increases skeletal muscle metabolism and can cause hyperthermia.[11] The pathophysiological mechanism of malignant hyperthermia associated with the use of succinylcholine and halogenated, genetic mutation and altered cellular calcium metabolism is independent of thermoregulation.[12]

Thus, general anesthesia causes altered thermoregulation and hypothermia that follows a characteristic and progressive pattern.[313] During the first hour, the body temperature drops rapidly from 1–1.5°C (exponential phase). Later on (2–3 hours), the temperature drops slowly and continuously (linear phase) until it reaches a level where it stabilizes and no longer drops (plateau phase). Each phase corresponds to a different cause. The first phase is caused by heat redistribution from central to peripheral compartment due to the decrease in vasoconstrictor response threshold induced by anesthetic drugs. During this linear phase, heat loss exceeds metabolic production and the result is a net loss of heat. This decrease in boy temperature during surgery is mostly due to the radiation phenomena such as convection, evaporation, and conduction. The stabilization or plateau phase coincides with the launch of new thermoregulatory vasoconstriction that restores normal temperature gradient between the central and peripheral compartments.

The clinical effect of temperature variations induced by the surgical incision is unknown. It seems that for the same anesthetic concentration, to greatest is the surgical incision, the lower the threshold vasoconstrictor response.[3]

To be able to analyze the isolated effect of anesthetic drugs on thermoregulation, we need the performance of controlled studies, applying measurement methods of thermoregulation previously validated.

It has been described in patients with tumors related with the hypothalamus (suprasellar tumors, pituitary adenomas, and craniopharyngiomas) that both the tumor and surgical resection may lead to hypothalamic dysfunction and impaired thermoregulation.[14-17] Some studies[1415] show a shift in the hypothalamic regulation at 37.5°C and others[1617] show a higher incidence of alterations in thermoregulatory responses to heat (hyperthermia risk).

The pilot study of Chowdhury et al.[18] published in this issue of JSA, focuses on analyzing the effect of two anesthetic drugs, propofol and sevoflurane, on temperature changes in patients with pituitary pathology operated on in a transphenoid approach under general anesthesia. While the thermoregulatory response assessment made by the authors is indirect, from the point that temperature declines to the time of recovering, two interesting aspects of the study are worth noting: first, the dosage of propofol and sevoflurane are setted to obtain a pre-determined hypnotic effect,with BIS values ranging from 50 to 60. In a similar study by Ikeda et al.,[19] it could not be excluded that the greatest temperature drop induced by propofol versus sevoflurane in their patients could be the result of a comparatively high dosage of propofol. The second aspect of Chowdhury et al.'s study[18] is the consideration about the neuroanesthesic profile of propofol and sevoflurane beyond their effects on thermoregulation, as the impact of drugs on the coupling between cerebral blood flow and cerebral metabolic consumption of oxygen, their potential cerebral vasodilator effect, its influence on cerebral autoregulation, intracranial pressure, postoperative cognitive dysfunction, and its rapid induction and awakening are the issues that are all essential when choosing between an intravenous or inhalational anesthetic technique in neuroanesthesia.[20]

Evidence from experimental studies indicates that mild hypothermia, 32–34°C, has a protective effect against cerebral ischemia.[21] Current clinical evidence has only demonstrated the beneficial effects of therapeutic hypothermia in perinatal hypoxic encephalopathy[22] and after cardiac arrest.[23] However, it is clearly demonstrated that an increase in morbidity and mortality is associated with a drop in temperature below 36°C (myocardium complications, serious arrhythmias, impaired immune response, infection, surgical wound, increased bleeding and transfusion requirements, prolongation of hypnotic and muscle relaxants effects, thermal discomfort, postoperative shivering, and prolonged post-anesthesia recovery and hospital stay).[24] Notwithstanding this, worsening of neurological outcome has been referred from temperatures above 37.5°C in patients with neurological injury.[25]

In neuroanesthesia, the deleterious effects of mild hypothermia seem to outweigh its potential therapeutic benefits. It is essential, therefore, to consider several factors that affect thermoregulation in neurosurgical interventions, monitor temperature, and always have heating–cooling systems to ensure normothermia, not only during surgery but also postoperatively. It remains to determine the potential neuroprotective effects of decreases in temperature between 34°C and 36°C during neurosurgery.