Recent studies have shown that all general anaesthetics induce changes of body temperature thus inhibiting thermoregulation to some extent. In particular, the induction of anaesthesia inhibits tonic vasoconstriction and facilitates a core-to-peripheral redistribution of body heat, which is the major cause of core hypothermia during the first hour of anaesthesia [1-8].
Sedative doses of intravenous (i.v.) anaesthetics are commonly administered to dental patients to manage phobia associated with dentistry, or to reduce cardiovascular and mental distress during dental procedures. For such purposes, propofol provides reliable sedation and produces good operating conditions. Since propofol has the advantage of permitting easy adjustment of the degree of sedation and is associated with fast recovery , sedative (subanaesthetic) doses of the drug are also often given during regional anaesthesia.
We previously demonstrated the significant effects of sedative doses of benzodiazepines on autonomic nervous activity, e.g. body temperature, cutaneous blood flow and peripheral venous oxygen tension [10,11]. Therefore, we tested the hypothesis that low doses of propofol have effects on the core and peripheral skin temperature in male volunteers.
With the approval of the Ethics Committee of the School of Dental Medicine, Tsurumi University, we studied six healthy male volunteers aged 22-29 (mean ± SD; 23 ± 3) yr, weight 58-72 (64 ± 5) kg. None was obese, receiving medication or had a history of either thyroid disease or Raynaud's syndrome. Propofol was administered over 28 min at the following infusion rates: 8 mg kg−1 h−1 for the first 3 min, 4 mg kg−1 h−1 for the next 10 min and 2 mg kg−1 h−1 for the last 15 min.
Body temperature was measured at the following locations: the tympanic membrane for core temperature, and at other sites for peripheral skin temperature: the forehead, the forearm, the dorsum of the hand, as well as the fingertip. Disposable thermocouples connected to a digital temperature monitor (Model 6500, Mon-a-therm®; Mallinckrodt Anesthesiology Products, Inc., St Louis, MO, USA) were used. These thermometers require no user calibration and have a precision of 0.1°C when used with Mon-a-therm® disposable thermocouples. An aural probe was gently inserted until the volunteers reported feeling it touch the tympanic membrane. Each probe was then taped in place and the aural canal was occluded with cotton wool. Skin probes were taped in place at the four peripheral locations. Thermoregulatory vasoconstriction was evaluated using the gradient of the forearm temperature minus the fingertip temperature. A gradient of zero indicated the initiation of vasoconstriction .
We measured cutaneous blood flow on the dorsum of the hand and peripheral venous oxygen tension as indicators of vasoconstriction. The cutaneous blood flow of the dorsum of the hand was measured by a laser Doppler flowmeter (ALF21®; Advance Co., Tokyo, Japan). Peripheral venous oxygen tension was measured using blood drawn from the median vein of the forearm. The degree of sedation was judged by one of five grades according to the volunteer's response to having his name called out by a observer: 1: completely awake; 2: mild, awake but slightly drowsy; 3: moderately drowsy and response sluggish; 4: asleep, verbal response present, but very sluggish; and 5: marked sedation, asleep and not responding to verbal command. Arterial pressure, heart rate, SPO2 and respiratory rate were measured with a BP-508 monitor® (Nihon Kohrin Co., Tokyo, Japan). The volunteers' impressions concerning any alterations in their mood or sensation were recorded. Any complications observed during and immediately after the study were noted, together with any psychological phenomena.
Once the volunteers were in a supine position, venous catheters were inserted into veins in the antecubital fossae of both forearms - one was used to inject the propofol. The volunteers wore their own casual clothes according to the climate of the room, but if they felt cold, a towelling blanket was used to cover the lower half of the body. Values obtained before the start of the propofol infusion were defined as baseline.
All variables were recorded every 5 min over 90 min. Studies began at approximately 5.00 p.m. and finished near 7.00 p.m. The room temperature was maintained at approximately 24°C and the humidity between 50 and 60% throughout the experiment in a well-ventilated room.
Statistical comparisons were performed by one-way ANOVA, followed by a t-test with Bonferroni correction for all variables except for the degree of sedation, which was assessed by Wilcoxon signed rank sum test. Linear regression analysis compared (a) blood flow and venous oxygen tension with the forearm minus fingertip gradient and tympanic membrane temperature, and (b) venous oxygen tension with blood flow. All data (except degree of sedation) were expressed as mean ± SD. P < 0.05 was considered as significant.
Tympanic membrane and forehead temperatures decreased at 10 and 20 min after the start of the infusion, respectively, and reached a minimum at 30 min (−0.5 ± 0.2°C) and 40 min (−0.6 ± 0.2°C), respectively. These temperatures did not return to baseline for 90 min. Peripheral skin temperatures increased from the 10th to the 30th min at the forearm and fingertip, and from the 20th to the 30th min at the dorsum of the hand. These temperatures subsequently decreased (Fig. 1).
The forearm minus fingertip temperature gradient changed from negative to positive between the 30th and the 40th min, and then continuously increased (baseline −0.3 ± 0.4°C, 90 min: 6.5 ± 1.6°C) (Fig. 1). The cutaneous blood flow showed an increase from the 5th to the 40th min, after this time it began to decrease. Venous oxygen tension showed a trend of increasing from the 5th to the 20th min, and then began to decrease after 1 h.
The forearm minus fingertip temperature gradient negatively correlated with both blood flow (r = −0.38) and venous oxygen tension (r = −0.35). Tympanic membrane temperature also negatively correlated with blood flow (r = −0.66) and peripheral venous oxygen tension (r = −0.50). On the other hand, a positive correlation was observed between blood flow and venous oxygen tension (r = 0.46). No correlations were detected between tympanic membrane temperature and either blood flow or venous oxygen tension.
Heart rate, systolic and diastolic arterial pressure, and SPO2 decreased slightly from the 5th to the 30th min (Table 1). The level of sedation increased from the 5th to the 50th min (Table 2). Four volunteers complained of pain at the beginning of the propofol infusion. Five volunteers reported that they were pleasantly sedated and feeling relaxed, and one reported only drowsiness without a feeling of sedation. All volunteers recovered from sedation quickly. Five reported feeling cold upon emergence from sedation. However, neither shivering nor any other side-effects were observed.
Our major finding is that low doses of propofol increased peripheral skin temperature, blood flow in the dorsum of the hand, and decreased tympanic membrane temperature soon after the start of the infusion of the drug. These findings indicate that peripheral vasodilation had occurred, a process which is believed to correspond to initial redistribution hypothermia during general anaesthesia . Feelings of relaxation, or sedation, reduced sympathetic activity and promoted redistribution of heat through central or peripheral mechanisms. Thus, even at low doses, propofol impaired the tonic thermoregulatory vasoconstriction and provoked a core-to-peripheral redistribution of heat. In addition, the termination of the infusion resulted in a quick emergence from sedation, and a decrease of peripheral skin temperature, blood flow at the dorsum of the hand and of peripheral venous oxygen tension, and a slight increase in tympanic membrane temperature. A change in the skin temperature gradient - from negative to positive - was also observed. These findings demonstrate that vasoconstriction had occurred: thus, heat was no longer lost from the peripheries during emergence from sedation.
The effect of propofol on body temperature during general anaesthesia has been studied by Leslie and colleagues  and Matsukawa and colleagues . They reported that propofol caused a decrease in the vasoconstriction threshold. Ikeda and colleagues reported that the core temperature of patients who received propofol i.v. for the induction of anaesthesia were consistently lower than those of patients who had received only sevoflurane by inhalation. They suggested that strong vasodilation induced by propofol was responsible for this difference . In the present study, the large positive skin gradient observed upon emergence from sedation indicates that propofol has a pronounced effect on vasodilation. The observed gradient here was comparable with those reported by Kurz and colleagues, which was measured upon emergence from isoflurane anaesthesia . Ikeda and colleagues speculated that a brief period of systemic vasodilation induced by propofol was responsible for the hypothermia . We believe that this vasodilation may account, in part, for the later vasoconstriction. However, the rapid emergence from anaesthesia most likely activates autonomic nervous activity and produces strong vasoconstriction. Clinically, patients often complain about feelings of chill when recovering from propofol sedation, as observed in our volunteers. Since Tayefeh and colleagues speculated that vasoconstriction may facilitate deep vein thrombosis , the patient should be kept warm to minimize the risk of such complications.
Skin blood flow increased immediately after the start of the propofol infusion and decreased upon emergence from sedation. Furthermore, the peripheral venous oxygen tension decreased after 60 min. Both values correlated with the skin temperature gradient, indicating that they reflected changes in vascular tone. They also correlated with tympanic membrane temperature, but not with the absolute tympanic membrane temperature. These data indicate that the thermoregulatory response is not determined simply by core temperature, but may depend on the direction of core temperature changes . Dermal sympathomimetic vasoconstriction nerves are predominantly distributed to arteriovenous shunts. Therefore, blood flow is also controlled by sympathomimetic activity, as is body heat homeostasis. Robinson and colleagues reported that inhibition of sympathetic vasoconstriction was responsible for the decrease in arterial pressure in response to propofol administration rather than a direct action on vascular smooth muscles .
Arteriovenous shunts play an important role in maintaining body heat homeostasis. These shunts react quickly to heat production and diffusion. The skin surface gradient is considered an index of arteriovenous shunt perfusion . In the present study, the peripheral venous oxygen tension correlated with the skin-surface gradient, tympanic membrane temperature and blood flow. Hence, peripheral venous oxygen tension reflected changes in the perfusion through arteriovenous shunts: Tayefeh and colleagues reported an increase in peripheral venous oxygen tension due to thermoregulatory vasodilation .
When an anaesthetic dose of propofol is administered, blood pressure decreases immediately, although a sedative dose of propofol does not cause such a profound and prompt decrease in arterial pressure, as shown in the current study. Sedative doses of propofol might not be sufficient to cause the arteriolar dilation resulting from inhibition of sympathomimetic activity [15,16]. In contrast, blood flow and peripheral venous oxygen tension increased immediately after administration of the drug regardless of whether the dose was anaesthetic or sedative. These findings suggest that thermoregulatory changes occur even at low doses of propofol, which do not cause a decrease in arterial pressure.
Rubinstein and Sessler measured fingertip blood flow by volume plethysmography, and reported that the skin temperature gradient accurately reflected the arteriovenous shunt vasomotor status at the fingertip . Blood sampling for long periods from the fingertip or dorsum of the hand is difficult due to the strong vasoconstriction that occurs upon emergence from anaesthesia. For this reason, blood sampling from the antecubital fossa of the arm is recommended. Furthermore, as blood flow and peripheral venous oxygen tension are correlated, peripheral venous oxygen tension represents an alternative to blood flow measurement and an index of vasomotion when a blood flowmeter is unavailable.
In our previous papers [2-5,10,11], relatively small number of volunteers (n = 5-8) were evaluated since thermoregulatory mechanisms were supposed to be controlled tightly and the physiological variations should be quite small. Hence, we studied six volunteers in the current study.
In summary, propofol in low dose impairs tonic thermoregulatory vasoconstriction, and causes vasodilation during sedation and vasoconstriction upon emergence from sedation in male volunteers. Skin blood flow and peripheral venous oxygen tension are useful indicators for detecting the tone of peripheral vessels.
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Keywords:© 2002 European Academy of Anaesthesiology
ANAESTHESIA AND ANALGESIA, conscious sedation; BODY TEMPERATURE REGULATION; HAEMODYNAMICS, vasoconstriction; SEDATIVES, NON-BARBITURATE, propofol