Farzin Tayefeh

Dexmedetomidine Does Not Alter the Sweating Threshold, But Comparably and Linearly Decreases the Vasoconstriction and Shivering Thresholds

Background: Clonidine decreases the vasoconstriction and shivering thresholds. It thus seems likely that the alpha2 agonist dexmedetomidine will also impair control of body temperature. Accordingly, the authors evaluated the dose‐dependent effects of dexmedetomidine on the sweating, vasoconstriction, and shivering thresholds. They also measured the effects of dexmedetomidine on heart rate, blood pressures, and plasma catecholamine concentrations. Methods: Nine male volunteers participated in this randomized, double‐blind, cross‐over protocol. The study drug was administered by computer‐controlled infusion, targeting plasma dexmedetomidine concentrations of 0.0, 0.3, and 0.6 ng/ml. Each day, skin and core temperatures were increased to provoke sweating and then subsequently reduced to elicit vasoconstriction and shivering. Core‐temperature thresholds were computed using established linear cutaneous contributions to control of sweating, vasoconstriction, and shivering. The dose‐dependent effects of dexmedetomidine on thermoregulatory response thresholds were then determined using linear regression. Heart rate, arterial blood pressures, and plasma catecholamine concentrations were determined at baseline and at each threshold. Results: Neither dexmedetomidine concentration increased the sweating threshold from control values. In contrast, dexmedetomidine administration reduced the vasoconstriction threshold by 1.61 +/‐ 0.80 [degree sign] Celsius [center dot] ng sup ‐1 [center dot] ml (mean +/‐ SD) and the shivering threshold by 2.40 +/‐ 0.90 [degree sign] Celsius [center dot] ng sup ‐1 [center dot] ml. Hemodynamic responses and catecholamine concentrations were reduced from baseline values, but they did not differ at the two tested dexmedetomidine doses. Conclusions: Dexmedetomidine markedly increased the range of temperatures not triggering thermoregulatory defenses. The drug is thus likely to promote hypothermia in a typical hospital environment; it is also likely to prove an effective treatment for shivering.

Desflurane Slightly Increases the Sweating Threshold but Produces Marked, Nonlinear Decreases in the Vasoconstriction and Shivering Thresholds

Background Shivering is rare during general anesthesia. This observation suggests that anesthetics profoundly impair shivering. However, the effects of surgical doses of volatile anesthetics on control of shivering have yet to be evaluated. Furthermore, the effects of desflurane on sweating and thermoregulatory vasoconstriction remain unknown. Accordingly, the authors determined the concentration‐dependent effects of desflurane on sweating, vasoconstriction, and shivering.

Alfentanil blocks reflex pupillary dilation in response to noxious stimulation but does not diminish the light reflex

Background: Estimation of the micro‐agonist opioid effect in anesthetized and paralyzed patients is often imprecise and can be obscured by concomitant administration of drugs that affect the sympathetic nervous system, such as beta‐adrenergic blocking agents. As an alternative to hemodynamic measures of opioid effect, the authors tested the hypothesis that the pupillary light reflex or pupillary reflex dilation correlated with alfentanil concentrations during isoflurane anesthesia. Methods: Six volunteers were anesthetized on 4 days with 0.8% isoflurane. Alfentanil was administered intravenously to target total plasma concentrations of 0, 25, 50, and 100 ng/ml. A 5‐s tetanic electrical stimulus was applied to the skin. Pupil size and the pupillary light reflex were recorded before and after alfentanil administration, and before and for 8 min after the stimulus. Results: Alfentanil exponentially impaired reflex pupillary dilation, decreasing the maximum response amplitude from 5 mm at 0 ng/ml, to 2.3 mm at 25 ng/ml, to 1.0 mm at 50 ng/ml, and finally to 0.2 mm at 100 ng/ml. In contrast, only the highest concentration of alfentanil depressed the dilation of the pupil in the first 2 s after the stimulus. Alfentanil administration had no effect on the pupillary light reflex. Conclusions: Dilation of the pupil in response to a noxious stimulus is a measure of opioid effect in isoflurane‐anesthetized volunteers. In contrast, the pupillary light reflex is unaffected by alfentanil during isoflurane anesthesia. These data suggest that stimulus‐induced pupillary dilation may be used to evaluate the analgesic component of a combined volatile and opioid anesthetic.

Local radiant heating increases subcutaneous oxygen tension

BACKGROUND We evaluated a novel bandage that incorporates a thermostatically controlled radiant heater. We first determined optimal bandage temperature, based on increases in subcutaneous oxygen tension, a measure correlating well with resistance to infection and wound strength. We then tested the hypothesis that prolonged radiant heating would increase collagen deposition in experimental thigh wounds. METHODS The experimental bandages were positioned on the anterior thigh of 8 volunteers, and heated for 2 hours at 38 degrees C, 42 degrees C, or 46 degrees C, in a random order. Subcutaneous oxygen tension under the bandage was recorded from an electrode positioned within a subcutaneous tonometer. We studied 10 volunteers in the second protocol. For 1 week, the experimental bandage was continuously applied to one thigh, and heated to 38 degrees C using a 2-hour on/off cycle. On the alternate week, a standard gauze bandage was applied to the contralateral thigh. Treatment order was randomly assigned. Wound collagen deposition under each bandage was evaluated with subcutaneous polytetrafluoroethylene tubes, which were removed and assayed for hydroxyproline on the eighth day. Data are presented as means +/- SDs. RESULTS Skin temperature during heating ranged from 36 degrees C to 37.5 degrees C. Oxygen tension increased approximately 50% during heating, but the increase was comparable at the three tested temperatures. Even after heating was discontinued, subcutaneous oxygen tension remained elevated for the remaining 3 study hours. Collagen deposition after 1 week of active heating was 3.4 +/- 1.0 microg/ cm. After 1 week of control treatment, collagen deposition was 3.2 +/- 1.1 microg/cm (P = not significant). CONCLUSIONS Our data suggest that radiant heating at 38 degrees C significantly increases subcutaneous oxygen tension, and presumably resistance to infection. However, prolonged heating at this temperature does not increase wound collagen deposition.

Sympathetic nervous system does not mediate reflex pupillary dilation during desflurane anesthesia

Background Pupil size is determined by an interaction between the sympathetic and parasympathetic divisions of the autonomic nervous system. Noxious stimulation dilates the pupil in both unanesthetized and anesthetized humans. In the absence of anesthesia, dilation is primarily mediated by the sympathetic nervous system. In contrast, pupillary dilation in cats given barbiturate or cloralose anesthesia is mediated solely by inhibition of the midbrain parasympathetic nucleus. The mechanism by which noxious stimuli dilate pupils during anesthesia in humans remains unknown. Accordingly, the authors tested the hypothesis that the pupillary dilation in response to noxious stimulation during desflurane anesthesia is primarily a parasympathetic reflex. Methods In six volunteers, the alpha‐1 adrenergic receptors of the iris musculature were blocked by unilateral administration of topical dapiprazole; six other volunteers were given unilateral topical tropicamide to block the muscarinic receptors in the iris. Desflurane anesthesia was subsequently induced in all volunteers. Sympathetic nervous system activation, with reflex dilation of the pupil, was produced by noxious electrical stimulation during 4% and 8% end‐tidal desflurane, and by a rapid 4%‐to‐8% step‐up in the desflurane concentration. Pupil diameter and the change in pupil size induced by a light stimulus (light reflex amplitude) were measured with infrared pupillometry. Results Dapiprazole drops produced a Horners miosis, but pupils were equally small after induction of anesthesia. Pupillary dilation after noxious stimulation and desflurane step‐up was identical in the unblocked and dapiprazole‐blocked pupils. After tropicamide administration, the pupil was dilated and the light reflex was completely inhibited. Noxious stimulation nonetheless produced a slight additional dilation. Conclusions During desflurane anesthesia, pupillary dilation in response to noxious stimulation or desflurane step‐up is not mediated by the sympathetic nervous system (as it is in unanesthetized persons). Although inhibition of the pupillo‐constrictor nucleus may be the cause of this dilation, the mechanism remains unknown.

Meperidine and alfentanil do not reduce the gain or maximum intensity of shivering.

Background Thermoregulatory shivering can be characterized by its threshold (triggering core temperature), gain (incremental intensity increase with further core temperature deviation), and maximum intensity. Meperidine (a combined micro‐ and kappa‐agonist) treats shivering better than equianalgesic doses of pure micro‐opioid agonists. Meperidines special antishivering action is mediated, at least in part, by a disproportionate decrease in the shivering threshold. That is, meperidine decreases the shivering threshold twice as much as the vasoconstriction threshold, whereas alfentanil (a pure micro‐agonist) decreases the vasoconstriction and shivering thresholds comparably. However, reductions in the gain or maximum shivering intensity might also contribute to the clinical efficacy of meperidine. Accordingly, we tested the hypothesis that meperidine reduces the gain and maximum intensity of shivering much more than alfentanil does. Methods Ten volunteers were each studied on three separate days: (1) control (no drug); (2) a target total plasma meperidine concentration of 1.2 micro gram/ml; and (3) a target plasma alfentanil concentration of 0.2 micro gram/ml. Skin temperatures were maintained near 31 [degree sign] Celsius, and core temperatures were decreased by central‐venous infusion of cold lactated Ringers solution until maximum shivering intensity was observed. Shivering was evaluated using oxygen consumption and electromyography. A sustained increase in oxygen consumption identified the shivering threshold. The gain of shivering was calculated as the slope of the oxygen consumption versus core temperature regression, and as the slope of electromyographic intensity versus core temperature regression. Results Meperidine and alfentanil administration significantly decreased the shivering thresholds. However, neither meperidine nor alfentanil reduced the gain of shivering, as determined by either oxygen consumption or electromyography. Opioid administration also failed to significantly decrease the maximum intensity of shivering. Conclusions The authors could not confirm the hypothesis that meperidine reduces the gain or maximum intensity of shivering more than alfentanil does. These results suggest that meperidines special antishivering effect is primarily mediated by a disproportionate reduction in the shivering threshold.

Paralysis only slightly reduces the febrile response to interleukin-2 during isoflurane anesthesia

Background Fever sometimes occurs during anesthesia. However, it is rare considering how often pyrogenic causes are likely to be present and how fever is after surgery. This low incidence results in part from dose-dependent inhibition of fever by volatile anesthetics. Paralysis, however, may contribute by preventing shivering and the associated increase in metabolic heat production. Therefore the authors tested the hypothesis that paralysis during anesthesia decreases the febrile response to pyrogen administration. Methods Seven volunteers each participated on two study days. They were given 30 IU/g intravenous interleukin-2, followed 90 min later by an additional 70 IU/g dose. Anesthesia was induced 30 min after the second dose and maintained for 6 h with 0.6 minimum alveolar concentration isoflurane. The volunteers were randomly assigned to (1) paralysis with vecuronium or (2) no muscle relaxants. Body heat content and distribution were determined from measured tissue and skin temperatures. Data are presented as mean +/- SD; P < 0.05 was considered significant. Results There was no clinically important difference in peak core (tympanic membrane) temperatures on the unparalyzed (37.6 +/- 0.9 [degree sign]C) and paralyzed (37.2 +/- 0.6 [degree sign]C) days. Core heat content increased 1.2 +/- 0.7 kcal/kg over the last 5 h of anesthesia on the unparalyzed day, but only by 0.9 +/- 0.4 kcal/kg when the volunteers were paralyzed. Peripheral tissue heat content increased 0.1 +/- 1.1 kcal/kg on the unparalyzed day but decreased 1.1 +/- 0.7 kcal/kg when the volunteers were paralyzed. Consequently, body heat content increased 1.3 +/- 1.3 kcal/kg on the unparalyzed day but decreased significant by 0.2 +/- 0.8 kcal/kg when the volunteers were paralyzed. Conclusions Paralysis prevented shivering from increasing the metabolic rate. Consequently, body heat content decreased during paralysis, whereas otherwise it increased. Thermoregulatory vasoconstriction was nonetheless able to maintain similar peak and integrated core temperatures on each study day. Administration of muscle relaxants thus is not the primary explanation for the relative paucity of intraoperative fever.

Thermoregulatory vasodilation increases the venous partial pressure of oxygen.

Thermoregulatory arteriovenous shunt vasoconstriction may facilitate deep-vein thrombosis by producing relative venous stasis and hypoxia. Accordingly, we evaluated the effect of vasomotion on leg blood flow and venous oxygen tension. We studied five male volunteers, each of whom was warmed enough to trigger vasodilation and then cooled sufficiently to provoke thermoregulatory vasoconstriction. The process was then repeated during N2 O/desflurane anesthesia. Venous oxygen tension and saturation (with a fraction of inspired oxygen of 1.0) were evaluated in blood samples taken from a catheter that was inserted into a saphenous vein at the ankle and advanced until the tip was proximal to the knee. Thermoregulatory vasodilation with or without general anesthesia significantly increased arteriovenous shunt flow by approximately 10-fold, and increased total leg flow approximately sixfold. However, vasodilated flows were similar with and without general anesthesia, as were vasoconstricted flows. Before induction of anesthesia, thermoregulatory vasodilation increased venous oxygen tension from 46 +/- 6 to 187 +/- 99 mm Hg and venous saturation from 79% +/- 6% to 99% +/- 2%. After induction of anesthesia, thermoregulatory vasodilation increased venous oxygen tension from 55 +/- 11 to 356 +/- 103 mm Hg and venous saturation from 84% +/- 8% to 100% +/- 0%. Our data thus indicate that thermoregulatory vasodilation markedly increases both leg flow and venous oxygenation; and that both factors may help prevent perioperative venous thrombosis. Implications: Thermoregulatory arteriovenous shunt vasoconstriction may facilitate deep-vein thrombosis by producing related venous stasis and hypoxia. In male volunteers, the authors found that when vasodilation induced by warming was produced, both blood flow and venous oxygenation increased, both of which may help prevent perioperative venous thrombosis. (Anesth Analg 1997;85:657-62)

Lidocaine does not depress reflex dilation of the pupil

Background and Objectives. Pupillary dilation in response to dermatomal electrical stimulation is one method of determining sensory block level during combined epidural and general anesthesia. Use of this technique may, however, be confounded by systemic absorption of epidurally administered local anesthetics. Accordingly, the effects of intravenous lidocaine on the magnitude and duration of reflex pupillary dilation were evaluated. Methods. Six volunteers were each anesthetized twice with desflurane 3.5‐6.0%. During one anesthetic, intravenous lidocaine was administered to a plasma concentration of 5.3 ± 1.5 μg/mL. When the plasma concentrations were stable, a 5‐second tetanic electrical stimulus was applied. Pupil size was then recorded for 8 minutes. Results. Lidocaine, at plasma concentrations near 5 μg/mL, did not significantly alter the pupillary response to electrical stimulation. In contrast, stimulus‐induced increase in heart rate was obliterated. Painful stimulation did not increase systolic blood pressure in either case. Conclusions. Typical plasma lidocaine concentrations observed during epidural anesthesia are unlikely to prevent the use of pupillary responses to evaluate sensory block level.

Time-Dependent Changes in Heart Rate and Pupil Size During Desflurane or Sevoflurane Anesthesia

To better characterize alterations in autonomic function associated with prolonged anesthesia, we tested the hypothesis that the time-dependent effects of sevoflurane and desflurane differ. We studied seven male volunteers, each anesthetized for 8 h with 1.25 minimum alveolar anesthetic concentration desflurane on one study day and with 8 h sevoflurane on another. These volunteers did not undergo surgery and were minimally stimulated during the study. Measurements included blood pressure, heart rate, pupillary size and light reactivity, concentrations of serum catecholamines, and carbon dioxide production. Over time, heart rate and pupil size increased significantly. During 6 of the 14 anesthetics (45%), heart rate at some point exceeded 95 bpm; similarly, pupil size at some time exceeded 5 mm during 8 anesthetics (57%). In contrast, plasma catecholamine concentrations and carbon dioxide production remained unchanged, and blood pressure remained nearly constant. There are thus substantial time-dependent changes in autonomic functions during prolonged anesthesia, even in unstimulated, nonsurgical volunteers, but we could not detect a difference in these changes during desflurane compared with sevoflurane anesthesia. Implications: Pupil size and heart rate changes are used to guide the delivery of anesthesia. In volunteers, pupil size and heart rate increased with increasing duration of constant desflurane or sevoflurane anesthesia. Thus, anesthetic duration alters heart rate and pupil size independent of surgery and changes in anesthetic delivery. (Anesth Analg 1997;85:1362-6)