D. I. Sessler

Dexmedetomidine and Meperidine Additively Reduce the Shivering Threshold in Humans

Background and Purpose— Hypothermia might prove to be therapeutically beneficial in stroke victims; however, even mild hypothermia provokes vigorous shivering. Meperidine and dexmedetomidine each linearly reduce the shivering threshold (triggering core temperature) with minimal sedation. We tested the hypothesis that meperidine and dexmedetomidine synergistically reduce the shivering threshold without producing substantial sedation or respiratory depression. Methods— We studied 10 healthy male volunteers (18 to 40 years) on 4 days: (1) control (no drug); (2) meperidine (target plasma level 0.3 &mgr;g/mL); (3) dexmedetomidine (target plasma level 0.4 ng/mL); and (4) meperidine plus dexmedetomidine (target plasma levels of 0.3 &mgr;g/mL and 0.4 ng/mL, respectively). Lactated Ringer’s solution (≈4°C) was infused through a central venous catheter to decrease tympanic membrane temperature by ≈2.5°C/h; mean skin temperature was maintained at 31°C. An increase in oxygen consumption >25% of baseline identified the shivering threshold. Sedation was evaluated by using the Observer’s Assessment of Sedation/Alertness scale. Two-way repeated-measures ANOVA was used to identify interactions between drugs. Data are presented as mean±SD;P <0.05 was statistically significant. Results— The shivering thresholds on the study days were as follows: control, 36.7±0.3°C; dexmedetomidine, 36.0±0.5°C (P <0.001 from control); meperidine, 35.5±0.6°C (P <0.001); and meperidine plus dexmedetomidine, 34.7±0.6°C (P <0.001). Although meperidine and dexmedetomidine each reduced the shivering threshold, their interaction was not synergistic but additive (P =0.19). There was trivial sedation with either drug alone or in combination. Respiratory rate and end-tidal Pco2 were well preserved on all days. Conclusions— Dexmedetomidine and meperidine additively reduce the shivering threshold; in the small doses tested, the combination produced only mild sedation and no respiratory toxicity.

Anesthetic requirement is increased in redheads

Background:Age and body temperature alter inhalational anesthetic requirement; however, no human genotype is associated with inhalational anesthetic requirement. There is an anecdotal impression that anesthetic requirement is increased in redheads. Furthermore, red hair results from distinct mutations of the melanocortin-1 receptor. Therefore, the authors tested the hypothesis that the requirement for the volatile anesthetic desflurane is greater in natural redheaded than in dark-haired women. Methods:The authors studied healthy women with bright red (n = 10) or dark (n = 10) hair. Blood was sampled for subsequent analyses of melanocortin-1 receptor alleles. Anesthesia was induced with sevoflurane and maintained with desflurane randomly set at an end-tidal concentration between 5.5 and 7.5%. After an equilibration period, a noxious electrical stimulation (100 Hz, 70 mA) was transmitted through bilateral intradermal needles. If the volunteer moved in response to stimulation, desflurane was increased by 0.5%; otherwise, it was decreased by 0.5%. This was continued until volunteers “crossed over” from movement to nonmovement (or vice versa) four times. Individual logistic regression curves were used to determine desflurane requirement (P50). Desflurane requirements in the two groups were compared using Mann–Whitney nonparametric two-sample test; P < 0.05 was considered statistically significant. Results:The desflurane requirement in redheads (6.2 vol% [95% CI, 5.9–6.5]) was significantly greater than in dark-haired women (5.2 vol% [4.9–5.5]; P = 0.0004). Nine of 10 redheads were either homozygous or compound heterozygotes for mutations on the melanocortin-1 receptor gene. Conclusions:Red hair seems to be a distinct phenotype linked to anesthetic requirement in humans that can also be traced to a specific genotype.

Insufficiency in a New Temporal-Artery Thermometer for Adult and Pediatric Patients

SensorTouch™ is a new noninvasive temperature monitor and consists of an infrared scanner that detects the highest temperature on the skin of the forehead, presumably over the temporal artery. The device estimates core temperature (Tcore). We tested the hypothesis that the SensorTouch™ is sufficiently precise and accurate for routine clinical use. We studied adults (n = 15) and children (n = 16) who developed mild fever, a core temperature of at least 37.8°C, after cardiopulmonary bypass. Temperature was recorded at 15-min intervals throughout recovery with the SensorTouch™ thermometer and from the pulmonary artery (adults) or bladder (children). Pulmonary artery (Tcore) and SensorTouch™ (Tst) temperatures correlated poorly in adults: Tcore = 0.7 · Tst + 13, r2 = 0.3. Infrared and pulmonary artery temperatures differed by 1.3 ± 0.6°C; 89% of the adult temperatures thus differed by more than 0.5°C. Bladder and infrared temperatures correlated somewhat better in pediatric patients: Tcore = 0.9 · Tst + 12, r2 = 0.6. Infrared and bladder temperatures in children differed by only 0.3°C, but the sd of the difference was 0.5°C. Thus, 31% of the values in the infants and children differed by more than 0.5°C.

Intraoperative temperature monitoring sites in infants and children and the effect of inspired gas warming on esophageal temperature.

This study tested the hypotheses that 1) temperatures of “central” sites are similar in infants and children undergoing noncardiac surgery and 2) airway heating and humidification increases distal esophageal temperature. Twenty children were randomly assigned to receive 1) active airway humidification using an airway heater and humidifier set at 37°C (N = 8), 2) passive airway humidification using a heat and moisture exchanger (N = 6), or 3) no ainvay humidification and/or heating (control, N = 6). There were no statistically significant differences between tympanic membrane, esophageal, rectal, and axillary temperatures. The temperatures of the peripheral skin surface (forearm and fingertip) were significantly lower than tympanic membrane temperature and significantly different from each other. Although esophageal and tympanic membrane temperatures in the entire group were similar, esophageal temperatures in patients receiving active and passive airway humidification were about 0.35°C above tympanic temperatures after induction of anesthesia. In contrast, esophageal temperatures in patients without airway humidification were 0.25°C below tympanic temperatures after induction of anesthesia. Esophageal-tympanic membrane temperature differences in the patients given active and passive humidification differed significantly from the corresponding sum in the control group at all times, but not from each other.

Passive or active inspired gas humidification increases thermal steady-state temperatures in anesthetized infants.

We tested the hypothesis that active and passive airway humidification minimize hypothermia in infants, but that maintaining normothermia does not decrease the duration of postoperative recovery. A circle system was used to ventilate the lungs of anesthetized, intubated infants who were randomly assigned to active airway humidification and warming with use of an MR450 Servo airway heater and humidifier set at 37°C (n = 10), passive airway humidification with use of the Humid-Vent Mini heat and moisture exchanger placed between the Y-piece of the circle and the endotracheal tube (n = 10), or no airway humidification and heating (control, n = 10). Anesthesia was induced with thiopental and maintained with isoflurane and nitrous oxide in oxygen. The relative humidity of inspired respiratory gases was ∼35% in the control group and ∼90% in the group undergoing active airway humidification. Initial inspired humidity in the passive humidification group (45%) increased to ∼80% after 1 h of anesthesia. Humidity differed significantly across groups at all times (P ≤ 0.05). Steady-state rectal temperatures (100--120 min after induction) were 36.2 ± 0.7°C in patients given active humidification and heating, 35.7 ± 0.9°C in the passively humidified group, and 35.2 ± 0.4°C in the control group (P ≤ 0.05 between each group). Recovery from general anesthesia was rapid in all patients and did not correlate with central temperature changes or type of humidification (P = NS). We conclude that heat and moisture exchangers are less effective than active heating and humidification, but significantly better than no humidification.

Propofol Linearly Reduces the Vasoconstriction and Shivering Thresholds

Background Skin temperature is best kept constant when determining response thresholds because both skin and core temperatures contribute to thermoregulatory control. In practice, however, it is difficult to evaluate both warm and cold thresholds while maintaining constant cutaneous temperature. A recent study shows that vasoconstriction and shivering thresholds are a linear function of skin and core temperatures, with skin contributing 20 plus/minus 6% and 19 plus/minus 8%, respectively. (Skin temperature has long been known to contribute [nearly equal] 10% to the control of sweating.) Using these relations, we were able to experimentally manipulate both skin and core temperatures, subsequently compensate for the changes in skin temperature, and finally report the results in terms of calculated core‐ temperature thresholds at a single designated skin temperature. Methods Five volunteers were each studied on 4 days: (1) control; (2) a target blood propofol concentration of 2 micro gram/ml; (3) a target concentration of 4 micro gram/ml; and (4) a target concentration of 8 micro gram/ml. On each day, we increased skin and core temperatures sufficiently to provoke sweating. Skin and core temperatures were subsequently reduced to elicit peripheral vasoconstriction and shivering. We mathematically compensated for changes in skin temperature by using the established linear cutaneous contributions to the control of sweating (10%) and to vasoconstriction and shivering (20%). From these calculated core‐temperature thresholds (at a designated skin temperature of 35.7 degrees Celsius), the propofol concentration‐ response curves for the sweating, vasoconstriction, and shivering thresholds were analyzed using linear regression. We validated this new method by comparing the concentration‐dependent effects of propofol with those obtained previously with an established model. Results The concentration‐response slopes for sweating and vasoconstriction were virtually identical to those reported previously. Propofol significantly decreased the core temperature triggering vasoconstriction (slope = 0.6 plus/minus 0.1 degree Celsius *symbol* micro gram sup ‐1 *symbol* ml sup ‐1; r2 = 0.98 plus/minus 0.02) and shivering (slope = 0.7 plus/minus 0.1 degree Celsius *symbol* micro gram sup ‐1 *symbol* ml sup ‐1; r2 = 0.95 plus/minus 0.05). In contrast, increasing the blood propofol concentration increased the sweating threshold only slightly (slope = 0.1 plus/minus 0.1 degree Celsius *symbol* micro gram sup ‐1 *symbol* ml sup ‐1; r2 = 0.46 plus/minus 0.39). Conclusions Advantages of this new model include its being nearly noninvasive and requiring relatively little core‐temperature manipulation. Propofol only slightly alters the sweating threshold, but markedly reduces the vasoconstriction and shivering thresholds. Reductions in the shivering and vasoconstriction thresholds are similar; that is, the vasoconstriction‐to‐shivering range increases only slightly during anesthesia.