Martha Dechert

Meperidine decreases the shivering threshold twice as much as the vasoconstriction threshold

Background: Meperidine administration is a more effective treatment for shivering than equianalgesic doses of other opioids. However, it remains unknown whether meperidine also profoundly impairs other thermoregulatory responses, such as sweating or vasoconstriction. Proportional inhibition of vasoconstriction and shivering suggests that the drug acts much like alfentanil and anesthetics but possesses greater thermoregulatory than analgesic potency. In contrast, disproportionate inhibition would imply a special antishivering mechanism. Accordingly, the authors tested the hypothesis that meperidine administration produces a far greater concentration‐dependent reduction in the shivering than vasoconstriction threshold. Methods: Nine volunteers were each studied on three days: 1) control (no opioid); 2) a target total plasma meperidine concentration of 0.6 micro gram/ml (40 mg/h); and 3) a target concentration of 1.8 micro gram/ml (120 mg/h). Each day, skin and core temperatures were increased to provoke sweating and then subsequently reduced to elicit vasoconstriction and shivering. Core‐temperature thresholds (at a designated skin temperature of 34 degrees Celsius) were computed using established linear cutaneous contributions to control sweating (10%) and vasoconstriction and shivering (20%). The dose‐dependent effects of unbound meperidine on thermoregulatory response thresholds was then determined using linear regression. Results are presented as means +/‐ SDs. Results: The unbound meperidine fraction was [nearly equal] 35%. Meperidine administration slightly increased the sweating threshold (0.5 +/‐ 0.8 degrees Celsius [center dot] micro gram sup ‐1 [center dot] ml; r2 = 0.51 +/‐ 0.37) and markedly decreased the vasoconstriction threshold (‐3.3 +/‐ 1.5 degrees Celsius [center dot] micro gram sup ‐1 [center dot] ml; r sup 2 = 0.92 +/‐ 0.08). However, meperidine reduced the shivering threshold nearly twice as much as the vasoconstriction threshold (‐6.1 +/‐ 3.0 degrees Celsius [center dot] micro gram sup ‐1 [center dot] ml; r2 = 0.97 +/‐ 0.05; P = 0.001). Conclusions: The special antishivering efficacy of meperidine results at least in part from an uncharacteristically large reduction in the shivering threshold rather than from exaggerated generalized thermoregulatory inhibition. This pattern of thermoregulatory impairment differs from that produced by alfentanil, clonidine, propofol, and the volatile anesthetics, all which reduce the vasoconstriction and shivering thresholds comparably.

Heat balance and distribution during the core-temperature plateau in anesthetized humans

Background Once triggered, intraoperative thermoregulatory vasoconstriction is remarkably effective in preventing further hypothermia. Protection results from both vasoconstriction-induced decrease in cutaneous heat loss and altered distribution of body heat. However, the independent contributions of each mechanism have not been quantified. Accordingly, we evaluated overall heat balance and distribution of heat within the body during the core-temperature plateau.

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.

Midazolam minimally impairs thermoregulatory control

Perioperative hypothermia usually results largely from pharmacologic inhibition of normal thermoregulatory control.Midazolam is a commonly used sedative and anesthetic adjuvant whose thermoregulatory effects are unknown. We therefore tested the hypothesis that midazolam administration impairs thermoregulatory control. Eight volunteers were studied on 2 days each, once without drug and once at a target total plasma midazolam concentration of 0.3 micro gram/mL (corresponding to administration of approximate equals 40 mg over approximate equals 4 h). Each day, skin and core temperatures were increased sufficiently to provoke sweating, and then reduced to elicit peripheral vasoconstriction and shivering. We mathematically compensated for changes in skin temperature using the established linear cutaneous contributions to control of each response. From these calculated thresholds (core temperatures triggering responses at a designated skin temperature of 34 degrees C), we determined the thermoregulatory effects of midazolam. The sweating threshold was decreased approximate equals 0.3 degrees C by midazolam administration: 37.3 +/- 0.2 degrees C vs 37.0 +/- 0.3 degrees C (P = 0.0004, paired t-test). Midazolam decreased the core temperature that triggered vasoconstriction somewhat more: 37.1 +/- 0.2 degrees C vs 36.3 +/- 0.5 degrees C (P = 0.0002). Similarly, midazolam decreased the shivering threshold: 35.9 +/- 0.3 degrees C vs 35.3 +/- 0.6 degrees C (P = 0.03). The sweating-to-vasoconstriction (interthreshold) range, therefore, increased from 0.2 +/- 0.1 degrees C to 0.7 +/- 0.3 degrees C (P = 0.002). Although statistically significant, this relatively small increase contrasts markedly with the 3-5 degrees C interthreshold ranges produced by clinical doses of volatile anesthetics, propofol, and opioids. Thus, plasma concentrations of midazolam far exceeding those used routinely produce relatively little impairment of thermoregulatory control. (Anesth Analg 1995;81:393-8)

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.

Desflurane reduces the gain of thermoregulatory arteriovenous shunt vasoconstriction in humans

Background Thermoregulatory responses, such as arteriovenous shunt vasoconstriction, provide substantial protection against core hypothermia. A response can be characterized by its threshold (core temperature triggering response), gain (rate at which response intensity increases, once triggered), and maximum response intensity. Reduced gain decreases the efficacy of a thermoregulatory response at a given threshold because response intensity will increase more slowly than usual. The effects of general anesthesia on the gain of arteriovenous shunt vasoconstriction have not been reported. Accordingly, we tested the hypothesis that desflurane decreases the gain of centrally mediated vasoconstriction.

The effect of opioids on thermoregulatory responses in humans and the special antishivering action of meperidine.

In summary, both mu-receptor and combined mu/kappa-receptor opioids impair thermoregulatory control. Alfentanil, a pure mu-receptor agonist slightly increased the thresholds for sweating and markedly decreased the thresholds for vasoconstriction and shivering. However, the vasoconstriction-to-shivering range remained normal during alfentanil administration as it does during general anesthesia. Meperidine, a combined mu- and kappa-receptor agonist, also slightly increased the threshold for sweating and reduced the thresholds for vasoconstriction. However, meperidine reduced the shivering threshold twice as much as the vasoconstriction threshold, thus significantly increasing the vasoconstriction-to-shivering range. Furthermore, shivering during meperidine administration, once triggered, was of low intensity suggesting that the drug also decreased the gain of shivering. The special antishivering action of meperidine appears to result, at least in part, from its kappa-receptor activity.

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.