bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Duration and Temperature of Prewarming
Authors: Sessler Daniel I. , Schroeder Marc , Merrifield Benjamin , Matsukawa Takashi , Cheng Christi
Published: November 2003

Background

Core hypothermia developing immediately after induction of anesthesia results largely from an internal core-to-peripheral redistribution of body heat. Although difficult to treat, redistribution can be prevented by prewarming. The benefits of prewarming may be limited by sweating, thermal discomfort, and efficacy of the warming device. Accordingly, the optimal heater temperature and minimum warming duration likely to substantially reduce redistribution hypothermia were evaluated.

Methods

Sweating, thermal comfort, and extremity heat content were evaluated in seven volunteers. They participated on two study days, each consisting of a 2-h control period followed by 2 h of forced-air warming with the heater set on "medium" (approximately 40 degrees C) or "high" (approximately 43 degrees C). Arm and leg tissue heat contents were determined from 19 intramuscular needle thermocouples, ten skin temperatures, and "deep" foot temperature.

Results

Half the volunteers started sweating during the second hour of warming. None of the volunteers felt uncomfortably warm during the first hour of heating, but many subsequently did. With the heater set on "high," arm and leg heat content increased 69 kcal during the first 30 min of warming and 136 kcal during the first hour of warming, representing 38% and 75%, respectively, of the values observed after 2 h of warming. The increase was only slightly less when the heater was set to "medium."

Conclusions

Neither sweating nor thermal discomfort limited heat transfer during the first hour of warming. Thirty minutes of forced-air warming increased peripheral tissue heat content by more than the amount normally redistributed during the first hour of anesthesia. The large increase in arm and leg heat content during prewarming thus explains the observed efficacy of prewarming.
Analysis of Drug Interaction between Intrathecal Clonidine and MK-801 in Peripheral Neuropathic Pain Rat Model
Authors: Lee Youn-Woo , Yaksh Tony L.
Published: November 2003

Background

Spinally delivered alpha 2-adrenoceptor agonists and N-methyl-D-aspartate antagonists each have been shown to have actions attenuating the hyperesthesia in rat models of nerve injury pain. Using a fixed-dose analysis and an isobolographic paradigm, the spinal interaction between the alpha 2-adrenoceptor agonist clonidine and the N-methyl-D-aspartate antagonist MK-801 is characterized in a rat model of nerve injury-induced tactile hyperesthesia.

Methods

Male Sprague Dawley rats were anesthetized with halothane, and the left L5 and L6 spinal nerves were ligated (Chung model). After 7-10 days' recovery, a Polyethylene tubing catheter was implanted into the lumbar intrathecal space. After recovery from catheter implantations (5-7 days), intrathecal dose-response curves were established for the antihyperesthesia effects of clonidine (3, 6, 10, and 20 micrograms) and MK-801 (1, 3, 10, and 20 micrograms) alone to obtain the ED50 for each agent. In separate studies, three doses of clonidine (1, 3, and 10 micrograms) were injected mixed with one dose of MK-801 (1 microgram) for fixed-dose analysis, and three doses of the two agents (2, 6, and 20 micrograms) were injected jointly in a fraction of the dose ratio 1:1 for isobolographic analysis. Thresholds for left hind paw withdrawal to von Frey hair application were assessed.

Results

Rats with nerve ligation showed a reliable tactile hyperesthesia (mechanical threshold 1-3 g vs. normal > 15 g). Intrathecal clonidine and MK-801 alone produced dose-dependent reductions of tactile hyperesthesia: ED50 9 micrograms and 10 micrograms, respectively. With the fixed-dose analysis, the log dose-response curves showed a left shift that considerably exceeds the theoretical curve made by a simple sum of the effects of clonidine alone and with MK-801 (1 microgram). With the isobolographic analysis, the combination ED50 was found to be statistically less than the theoretical additive dose combination. Intrathecal atipamezole, an alpha 2 antagonist, reversed the effects of clonidine and the clonidine/MK-801 mixture but not MK-801 alone. The side effect of clonidine was sedation and urination and that of MK-801 was motor weakness at doses above 10 micrograms. These effects were considerably less severe in rats after equiactive doses in the combination group.

Conclusions

The neuropathic pain is mediated by low-threshold mechanoreceptors, sympathetically dependent, and sensitive to both alpha 2 agonists and N-methyl-D-aspartate antagonists. Intrathecal clonidine may act to diminish sympathetic outflow, whereas MK-801 blocks the N-methyl-D-aspartate receptor that is associated with other spinal systems related to pain transmission mechanism. The two separate mechanisms may account for the powerful synergy observed in this study. Such combinations might be useful in neuropathic pain states to potentiate the antihyperpathic effects and to reduce the side effects of each agents.
The Membrane Lipid Cholesterol Modulates Anesthetic Actions on a Human Brain Ion Channel
Authors: Rehberg Benno , Urban Bernd W. , Duch Daniel S.
Published: November 2003

Background

Molecular theories of general anesthesia often are divided into two categories: (1) Anesthetics may bind specifically to proteins, such as ionic channels, and alter their function directly, and (2) anesthetics may alter the functions of integral membrane proteins indirectly through modification of the physical properties of the membrane. Recent studies have provided evidence that anesthetics can bind to proteins and modify their function directly, bringing into question the role of the membrane in anesthetic interactions. To reexamine the role of membrane lipids in anesthetic interactions, an experimental approach was used in which the membrane lipid composition could be systematically altered and the impact on anesthetic interactions with potential targets examined.

Methods

Sodium channels from human brain cortex were incorporated into planar lipid bilayers with increasing cholesterol content. The anesthetic suppression of these channels by pentobarbital was quantitatively examined by single channel measurements under voltage-clamp conditions.

Results

Changes in cholesterol content had no effect on measured channel properties in the absence of anesthetic. In the presence of pentobarbital, however, cholesterol inhibited anesthetic suppression of channel ionic currents, with 1.9% (weight/weight, corresponding to 3.5 mol%) cholesterol decreasing anesthetic suppression of sodium channels by half.

Conclusions

These results support a critical role for the lipid membrane in some anesthetic actions and further indicate that differences in lipid composition must be considered in the interpretation of results when comparing the anesthetic potencies of potential targets in model systems.
Buccal Absorption of Fentanyl Is pH-Dependent in Dogs
Authors: Streisand James B , Zhang Jie , Niu Suyi , McJames Scott , Natte Remco , Pace Nathan L.
Published: November 2003

Background

Analgesia and sedation have been achieved noninvasively by fentanyl administration through the oral and nasal mucosa. In theory, the transmucosal bioavailability and absorption of fentanyl could be improved by converting more fentanyl to the unionized form by adjusting the surrounding pH. The authors tested this hypothesis in dogs.

Methods

Under general anesthesia, each of six mongrel dogs was given fentanyl on repeated occasions, first intravenously (once), then by application to the buccal mucosa (six times). Buccal fentanyl administration was accomplished by placement of a pH-buffered solution of fentanyl into a specially constructed cell, which was clamped to the dog's buccal mucosa for 60 min. Fentanyl solutions with pHs of 6.6, 7.2, and 7.7 were studied to span a tenfold difference in the unionized fraction of fentanyl. Femoral arterial blood samples were sampled frequently and analyzed for fentanyl using a radioimmunoassay. Peak plasma concentration and the time of its occurrence for each buccal study were noted from the plasma concentration verses time profile. Terminal elimination half-life, bioavailability, and permeability coefficients were calculated using standard pharmacokinetic techniques.

Results

The variables peak plasma concentration, bioavailability, and permeability coefficient increased three- to fivefold as the pH of the fentanyl buccal solution increased and more fentanyl molecules became unionized. There was no difference in terminal elimination half-life after intravenous fentanyl (244 +/- 68 min) or buccal fentanyl administration (pH 7.7, 205 +/- 89 min; pH 7.2, 205 +/- 65 min; pH 6.6, 196 +/- 48 min). In all buccal studies regardless of pH, time to peak plasma concentration occurred within 10 min of removal of the fentanyl solutions from the buccal mucosa.

Conclusions

The buccal absorption, bioavailability, and permeability of fentanyl are markedly increased as the pH of the fentanyl solution becomes more basic. Most likely, this is because of an increase in the fraction of unionized fentanyl.
Cervical Spine Movement during Laryngoscopy with the Bullard, Macintosh, and Miller Laryngoscopes
Authors: Hastings Randolph H. , Vigil A. Christopher , Hanna Richard , Yang Bor-Yau , Sartoris David J.
Published: November 2003

Background

Direct laryngoscopy requires movement of the head, neck, and cervical spine. Spine movement may be limited for anatomic reasons or because of cervical spine injury. The Bullard laryngoscope, a rigid fiberoptic laryngoscope, may cause less neck flexion and head extension than conventional laryngoscopes. The purpose of this study was to compare head extension (measured externally), cervical spine extension (measured radiographically), and laryngeal view obtained with the Bullard, Macintosh, and Miller laryngoscopes.

Methods

Anesthesia was induced in 35 ASA 1-3 elective surgery patients. Patients lay on a rigid board with head in neutral position. Laryngoscopy was performed three times, changing between the Bullard, Macintosh, and Miller laryngoscopes. Head extension was measured with an angle finder attached to goggles worn by the patient. The best laryngeal view with each laryngoscope was assessed by the laryngoscopist. In eight patients, lateral cervical spine radiographs were taken before and during laryngoscopy with the Bullard and Macintosh blades.

Results

Median values for external head extension were 11 degrees, 10 degrees, and 2 degrees with the Macintosh, Miller, and Bullard laryngoscopy (P < 0.01), respectively. Significant reductions in radiographic cervical spine extension were found for the Bullard compared to the Macintosh blade at the atlantooccipital joint, atlantoaxial joint, and C3-C4. Median atlantooccipital extension angles were 6 degrees and 12 degrees for the Bullard and Macintosh laryngoscopes, respectively. The larynx could be exposed in all patients with the Bullard but only in 90% with conventional laryngoscope (P < 0.01).

Conclusions

The Bullard laryngoscope caused less head extension and cervical spine extension than conventional laryngoscopes and resulted in a better view. It may be useful in care of patients in whom cervical spine movement is limited or undesirable.
Does Spinal Anesthesia Result in a More Complete Sympathetic Block Than That from Epidural Anesthesia?
Authors: Stevens Rom A. , Beardsley David , White J. Lee , Kao Tzu-Cheg , Gantt Rod , Holman Stephen
Published: November 2003

Background

Spinal and epidural injection of local anesthetics are used to produce sympathetic block to diagnose and treat certain chronic pain syndromes. It is not clear whether either form of regional anesthesia produces a complete sympathetic block. Spinal anesthesia using tetracaine has been reported to produce a decrease in plasma catecholamine concentrations. This has not been demonstrated for epidural anesthesia in humans with level of anesthesia below C8. One possible explanation is that spinal anesthesia results in a more complete sympathetic block than epidural anesthesia. To examine this question, a cross-over study was performed in young, healthy volunteers.

Methods

Ten subjects underwent both spinal and epidural anesthesia with lidocaine (plain) on the same day with complete recovery between blocks. By random assignment, spinal anesthesia and epidural anesthesia were induced via lumbar injection. Before and 30 min after local anesthetic injection, a cold pressor test (CPT) was performed. Blood was obtained to determine epinephrine and norepinephrine plasma concentrations at four stages: (1) 20 min after placing peripheral catheters, (2) at the end of a 2-min CPT (before conduction block), (3) 30 min after injection of epidural or spinal lidocaine, and (4) at the end of a second CPT (during anesthesia). Mean arterial pressure, heart rate, noninvasive cardiac index, and analgesia to pin-prick were monitored.

Results

Neither spinal nor epidural anesthesia changed baseline resting values of catecholamines or any hemodynamic variable, except heart rate, which was slightly decreased during spinal anesthesia. Median level of analgesia was T4 during spinal and T3 during epidural anesthesia. CPT before conduction block reliably increased heart rate, mean arterial pressure, cardiac index, epinephrine, and norepinephrine. Conduction block attenuated the increase in response to CPT only in mean arterial pressure (spinal and epidural) and cardiac index (spinal only). Neither technique blocked the increase in heart rate, norepinephrine, or epinephrine to CPT.

Conclusions

Spinal anesthesia did not result in a more complete attenuation of the sympathetic response to a CPT than did epidural anesthesia. In response to the CPT, spinal anesthesia blocked the increase in cardiac index, and epidural anesthesia resulted in a decrease in total peripheral resistance compared to the pre-anesthesia state. The differences between the techniques are not significant and are of uncertain clinical implications.
A Comparison of Baroreflex Sensitivity during Isoflurane and Desflurane Anesthesia in Humans
Authors: Muzi Michael , Ebert Thomas J.
Published: November 2003

Background

Desflurane anesthesia has been associated with heart rate (HR) and sympathetic nerve activity (SNA) responses that differ from those during isoflurane anesthesia. Whether these differences might be due to better preservation by desflurane of the baroreceptor reflex control of HR or SNA in humans was examined.

Methods

Baroreflex sensitivity was assessed in 18 volunteers anesthetized with either desflurane or isoflurane. Measurements of HR, blood pressure (BP), and efferent SNA (percutaneous recordings from the peroneal nerve) were made, and baroreflex sensitivity was evaluated at conscious baseline and during 0.5, 1.0, and 1.5 MAC anesthesia. Baroreflex responses were triggered by bolus intravenous injections of nitroprusside (100 micrograms) and phenylephrine (150 micrograms). The linear portions of the baroreflex curves relating HR to mean arterial pressure and relating SNA to diastolic pressure were determined to obtain cardiac and sympathetic baroslopes, respectively.

Results

Cardiac (HR) baroslopes were equally diminished at increasing MAC of both anesthetics. Sympathetic baroslopes were preserved at 0.5 MAC isoflurane but diminished at 0.5 MAC desflurane. Higher MAC produced equal depression of sympathetic baroslopes with both anesthetics.

Conclusions

Increasing MAC of desflurane and isoflurane anesthesia results in similar and progressive decreases in BP but dissimilar SNA and HR responses. These differences are not explained by disparate effects of these anesthetics on the baroreceptor reflex control of SNA or HR.
Abnormal Action Potential Responses to Halothane in Heart Muscle Isolated from Malignant Hyperthermia-susceptible Pigs
Authors: Roewer Norbert , Greim Clemens , Rumberger Eckhart , Schulte am Esch Jochen
Published: November 2003

Background

During human and porcine malignant hyperthermia (MH), cardiac dysrhythmias and altered myocardial function can be observed. It is unknown whether a primary abnormality in cardiac muscle contributes to the cardiac symptoms during MH. An abnormal response to halothane has recently been demonstrated in action potentials (APs) from MH-susceptible (MHS) human skeletal muscles. We investigated the electrophysiologic properties in trabeculae isolated from the right ventricles of normal (MHN) and MHS pigs.

Methods

The experiments were performed on electrically stimulated (1 Hz) trabeculae isolated from the right ventricles of MHS and MHN pigs. Resting membrane potentials, APs, and tension were measured with and without the presence of 1% halothane. In addition, the halothane-equilibrated muscles were exposed to caffeine in increasing doses (1, 2, and 4 mM).

Results

In the absence of halothane, resting potential and AP characteristics in MHS and MHN muscles did not differ significantly. Halothane did not alter resting potentials but produced different alterations in the APs in MHS and MHN muscles, whereas the decrease in twitch tension was identical. In contrast to reductions in the AP amplitude and duration in MHN muscle, halothane produced an enlargement of the APs in MHS muscle. The addition of caffeine caused nearly identical prolongations of AP duration in MHS and MHN muscles.

Conclusions

This in vitro study demonstrates that halothane produces abnormal alterations in the dynamic electric properties of the ventricular excitable membrane from MHS pigs. These results suggest a latent defect in the myocardium of MHS pigs that becomes apparent in the presence of MH-triggering agents.
pH-Stat Management Reduces the Cerebral Metabolic Rate for Oxygen during Profound Hypothermia (17 degrees Celsius)
Authors: Hindman Bradley J. , Dexter Franklin , Cutkomp Johann , Smith Tom
Published: November 2003

Background

Greater cerebral metabolic suppression may increase the brain's tolerance to ischemia. Previous studies examining the magnitude of metabolic suppression afforded by profound hypothermia suggest that the greater arterial carbon dioxide tension of pH-stat management may increase metabolic suppression when compared with alpha-stat management.

Methods

New Zealand White rabbits, anesthetized with fentanyl and diazepam, were maintained during cardiopulmonary bypass (CPB) at a brain temperature of 17 degrees C with alpha-stat (group A, n = 9) or pH-stat (group B, n = 9) management. Measurements of brain temperature, systemic hemodynamics, arterial and cerebral venous blood gases and oxygen content, cerebral blood flow (CBF) (radiolabeled microspheres), and cerebral metabolic rate for oxygen (CMRO2) (Fick) were made in each animal at 65 and 95 min of CPB. To control for arterial pressure and CBF differences between techniques, additional rabbits underwent CPB at 17 degrees C. In group C (alpha-stat, n = 8), arterial pressure was decreased with nitroglycerin to values observed with pH-stat management. In group D (pH-stat, n = 8), arterial pressure was increased with angiotensin II to values observed with alpha-stat management. In groups C and D, CBF and CMRO2 were determined before (65 min of CPB) and after (95 min of CPB) arterial pressure manipulation.

Results

In groups A (alpha-stat) and B (pH-stat), arterial pressure; hemispheric CBF (44 +/- 17 vs. 21 +/- 4 ml.100 g-1.min-1 [median +/- quartile deviation]; P = 0.017); and CMRO2 (0.54 +/- 0.13 vs. 0.32 +/- 0.10 ml O2 x 100 g-1.min-1; P = 0.0015) were greater in alpha-stat than in pH-stat animals, respectively. As a result of arterial pressure manipulation, in groups C (alpha-stat) and D (pH-stat) neither arterial pressure (75 +/- 2 vs. 78 +/- 2 mmHg) nor hemispheric CBF (40 +/- 10 vs. 48 +/- 6 ml.100 g-1.min-1; P = 0.21) differed between alpha-stat and pH-stat management, respectively. Nevertheless, CMRO2 was greater in alpha-stat than in pH-stat animals (0.71 +/- 0.10 vs. 0.45 +/- 0.10 ml O2 x 100g-1.min-1, respectively; P = 0.002).

Conclusions

At 17 degrees C, CMRO2 with pH-stat management is 35-40% less than that with alpha-stat management and is independent of CBF or arterial pressure differences between the techniques.
Neurologic Evaluation of the Rat during Sciatic Nerve Block with Lidocaine
Authors: Thalhammer J. G. , Vladimirova M. , Bershadsky B. , Strichartz G. R.
Published: November 2003

Background

Quantitative behavioral testing is necessary to establish a reproducible measure of differential functional blockade during regional anesthesia. Methods for assessment of the neurologic status (mental status, posture, gait, proprioception, motor function, autonomic function, and nociception) in veterinary neurology were adapted for the rat and used to monitor functional changes separately during a sciatic nerve block.

Methods

Sprague-Dawley rats were acclimated to laboratory routine before the study so that lidocaine (0.1 ml, 1%) could be injected near the sciatic notch without any chemical restraint. The onset, duration, and magnitude of functional losses were monitored. Proprioceptive integrity was evaluated by assessing the response to tactile placing and the hopping response. Extensor postural thrust, a test for postural reactions in small animals, was assessed on a digital balance and found adequate for quantifying motor function. Analgesia was assessed by measuring withdrawal response latencies to noxious thermal stimulation (51 degrees C) and to superficial and deep noxious pinches. Autonomic function was monitored by measuring skin temperature. Contralateral limb function was used as an internal control, and injection of saline was used as an external control in separate, control animals.

Results

Onset of postural and gait abnormalities were observed as early as 40 s after injection. On each occasion proprioceptive impairment was detected first, followed by impairment of motor function and nociception. Complete absence of proprioception occurred from 10 to 30 min (n = 9) and of motor function at 30 min after injection (n = 10); both functions were fully recovered by 120 min. A unilateral increase in skin temperature on the foot was detected by 1 min; had reached its maximum change, 5.3 +/- 0.7 degrees C, at 10 min; and had returned to control levels at 60 min after injection (n = 12). Withdrawal response to cutaneous or superficial pain was absent in all ten animals from 5 to 30 min whereas the response to deep pain was absent in all ten animals at 20 min only. The response to noxious stimulation recovered at 90 min. Attention was paid to the temporal relation of the impairment of various functions.

Conclusions

Quantitative observations of the onset, offset, and intensity of differential functional impairment or block over time will make it possible to establish the doses and conditions for local anesthetics that result in differential nerve block and will permit comparison of these changes among different drugs and "clinical" protocols.
Dexmedetomidine Premedication Attenuates Ketamine-induced Cardiostimulatory Effects and Postanesthetic Delirium
Authors: Levanen Jaakko , Makela Marja-Leena , Scheinin Harry
Published: November 2003

Background

Dexmedetomidine is a new potent and highly selective alpha 2-adrenoceptor agonist with sedative-hypnotic and anesthetic sparing properties. Because of its sympathoinhibitory activity, it may prove useful in balancing the cardiostimulatory effects and attenuating the adverse central nervous system effects of ketamine.

Methods

A double-blind, randomized and comparative parallel-group study design was employed in 40 volunteers with ASA physical status 1 who were scheduled for elective superficial surgery under ketamine anesthesia. Dexmedetomidine (2.5 micrograms/kg, n = 20) or midazolam (0.07 mg/kg, n = 20) was administered intramuscularly 45 min before induction of anesthesia. Anesthesia was induced with 2 mg/kg ketamine intravenously, and muscle relaxation was achieved with vecuronium. After tracheal intubation, anesthesia was maintained with nitrous oxide/oxygen (2:1) and additional 1 mg/kg intravenous ketamine boluses according to clinical and cardiovascular criteria. Hypotension and bradycardia were treated by increasing the intravenous infusion rate of crystalloids and intravenous atropine, respectively. Sedative and anxiolytic properties, intra- and postoperative drug requirements, psychomotor and cognitive impairments, and cardiovascular effects were compared between the two groups.

Results

Dexmedetomidine and midazolam proved to have equal sedative and anxiolytic effects after intramuscular administration, but dexmedetomidine induced significantly less preoperative psychomotor impairment and less anterograde amnesia than did midazolam. Compared to midazolam, dexmedetomidine decreased the need for intraoperative ketamine and was more effective in reducing ketamine-induced adverse central nervous system effects. Dexmedetomidine also was superior to midazolam in attenuating the hemodynamic responses to intubation and the cardiostimulatory effects of ketamine in general, but it increased the incidence of intra- and postoperative bradycardia.

Conclusions

These results suggest that premedication with 2.5 micrograms/kg dexmedetomidine is effective in attenuating the cardiostimulatory and postanesthetic delirium effects of ketamine. However, because of its propensity to cause bradycardia, routine use of an anticholinergic drug should be considered.
Oral Clonidine Premedication Blunts the Heart Rate Response to Intravenous Atropine in Awake Children
Authors: Nishina Kahoru , Mikawa Katsuya , Maekawa Nobuhiro , Obara Hidefumi
Published: November 2003

Background

Clonidine, which is known to have analgesic and sedative properties, has recently been shown to be an effective preanesthetic medication in children. The drug may cause side effects, including bradycardia and hypotension. This study was conducted to evaluate the ability of intravenous atropine to increase the heart rate (HR) in awake children receiving clonidine preanesthetic medication.

Methods

We studied 96 otherwise healthy children, 8-13 yr old, undergoing minor surgery. They received, at random, oral clonidine 2 or 4 micrograms.kg-1 or placebo 105 min before scheduled induction of anesthesia. Part I (n = 48, 16 per group): When hemodynamic parameters after insertion of a venous catheter had been confirmed to be stable, atropine was administered in incremental doses of 2.5, 2.5, and 5 micrograms.kg-1 every 2 min. The HR and blood pressure were recorded at 1-min intervals. Part II (n = 48, 16 per group): After the recording of baseline hemodynamic values, successive doses of atropine (5 micrograms.kg-1 every 2 min, to 40 micrograms.kg-1), were administered until HR increased by 20 beats.min-1. The HR and blood pressure were recorded at 1-min intervals.

Results

Part I: The increases in HR in response to a cumulative dose of atropine 10 micrograms.kg-1 were 33 +/- 3%, 16 +/- 3%, and 8 +/- 2% (mean +/- SEM) in children receiving placebo, clonidine 2 micrograms.kg-1, and clonidine 4 micrograms.kg-1, respectively (P < 0.05). Part II: The HR in the control group increased by more than 20 beats.min-1 in response to atropine 20 micrograms.kg-1 or less. In two patients in the clonidine 4 micrograms.kg-1 group, HR did not increase by 20 beats.min-1 even after 40 micrograms.kg-1 of atropine.

Conclusions

Oral clonidine premedication (4 micrograms.kg-1) blunted the increase in HR after intravenous atropine in awake children, although clonidine 2 micrograms.kg-1 did not. A larger dose of atropine was required to increase the HR by 20 beats.min-1 in children receiving the premedicant in the larger dose.
Increasing Mean Skin Temperature Linearly Reduces the Core- temperature Thresholds for Vasoconstriction and Shivering in Humans
Authors: Cheng Christi , Matsukawa Takashi , Sessler Daniel I. , Makoto Ozaki , Kurz Andrea , Merrifield Benjamin , Lin Hank , Olofsson Par
Published: November 2003

Background

The contribution of mean skin temperature to the thresholds for sweating and active precapillary vasodilation has been evaluated in numerous human studies. In contrast, the contribution of skin temperature to the control of cold responses such as arteriovenous shunt vasoconstriction and shivering is less well established. Accordingly, the authors tested the hypothesis that mean skin and core temperatures are linearly related at the vasoconstriction and shivering thresholds in men. Because the relation between skin and core temperatures might vary by gender, the cutaneous contribution to thermoregulatory control also was determined in women.

Methods

In the first portion of the study, six men participated on 5 randomly ordered days, during which mean skin temperatures were maintained near 31, 34, 35, 36, and 37 degrees C. Core hypothermia was induced by central venous infusion of cold lactated Ringer's solution sufficient to induce peripheral vasoconstriction and shivering. The core-temperature thresholds were then plotted against skin temperature and a linear regression fit to the values. The relative skin and core contributions to the control of each response were calculated from the slopes of the regression equations. In the second portion of the study, six women participated on three randomly ordered days, during which mean skin temperatures were maintained near 31, 35, and 37 degrees C. At each designated skin temperature, core hypothermia sufficient to induce peripheral vasoconstriction and/or shivering was again induced by central venous infusion of cold lactated Ringer's solution. The cutaneous contributions to control of each response were then calculated from the skin- and core-temperature pairs at the vasoconstriction and shivering thresholds.

Results

There was a linear relation between mean skin and core temperatures at the response thresholds in the men: r = 0.90 +/- 0.06 for vasoconstriction and r = 0.94 +/- 0.07 for shivering. Skin temperature contributed 20 +/- 6% to vasoconstriction and 19 +/- 8% to shivering. Skin temperature in the women contributed to 18 +/- 4% to vasoconstriction and 18 +/- 7% to shivering, values not differing significantly from those in men. There was no apparent correlation between the cutaneous contributions to vasoconstriction and shivering in individual volunteers.

Conclusions

These data indicate that skin and core temperatures contribute linearly to the control of vasoconstriction and shivering in men and that the cutaneous contributions average approximately 20% in both men and women. The same coefficients thus can be used to compensate for experimental skin temperature manipulations in men and women. However, the cutaneous contributions to each response vary among volunteers; furthermore, the contributions to the two responses vary within volunteers.
Propofol Linearly Reduces the Vasoconstriction and Shivering Thresholds
Authors: Matsukawa Takashi , Kurz Andrea , Sessler Daniel I. , Bjorksten Andrew R. , Merrifield Benjamin , Cheng Christi
Published: November 2003

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 +/- 6% and 19 +/- 8%, respectively. (Skin temperature has long been known to contribute approximately 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 micrograms/ml; (3) a target concentration of 4 micrograms/ml; and (4) a target concentration of 8 micrograms/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 C), 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 +/- 0.1 degrees C.micrograms-1.ml-1; r2 = 0.98 +/- 0.02) and shivering (slope = -0.7 +/- 0.1 degrees C.micrograms -1.ml-1; r2 = 0.95 +/- 0.05). In contrast, increasing the blood propofol concentration increased the sweating threshold only slightly (slope = 0.1 +/- 0.1 degrees C.micrograms -1.ml-1; r2 = 0.46 +/- 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.
Defining Quality of Perioperative Care by Statistical Process Control of Adverse Outcomes
Authors: Lagasse Robert S. , Steinberg Ellen S. , Katz Robert I. , Saubermann Albert J.
Published: November 2003

Background

Through peer review, we separated the contributions of system error and human (anesthesiologist) error to adverse perioperative outcomes. In addition, we monitored the quality of our perioperative care by statistically defining a predictable rate of adverse outcome dependent on the system in which practice occurs and respondent to any special causes for variation.

Methods

Traditional methods of identifying human errors using peer review were expanded to allow identification of system errors in cases involving one or more of the anesthesia clinical indicators recommended in 1992 by the Joint Commission on Accreditation of Healthcare Organizations. Outcome data also were subjected to statistical process control analysis, an industrial method that uses control charts to monitor product quality and variation.

Results

Of 13,389 anesthetics, 110 involved one or more clinical indicators of the Joint Commission on Accreditation of Healthcare Organizations. Peer review revealed that 6 of 110 cases involved two separate errors. Of these 116 errors, 9 (7.8%) were human errors and 107 (92.2%) were system errors. Attribute control charts demonstrated all indicators, excepting one (fulminant pulmonary edema), to be in statistical control.

Conclusions

The major determinant of our patient care quality is the system through which services are delivered and not the individual anesthesia care provider. Outcome of anesthesia services and perioperative care is in statistical control and therefore stable. A stable system has a measurable, communicable capability that allows description and prediction of the quality of care we provide on a monthly basis.
The Relation between Cerebral Metabolic Rate and Ischemic Depolarization
Authors: Nakashima Ken , Todd Michael M. , Warner David S.
Published: November 2003

Background

Reductions in cerebral metabolic rate may increase the brain's tolerance of ischemia. However, outcome studies suggest that reductions in cerebral metabolic rate produced by anesthetics and by hypothermia may not be equally efficacious. To examine this question, we measured the effects of hypothermia, pentobarbital, and isoflurane on the cerebral metabolic rate for glucose (CMRG) and on the time to the loss of normal membrane ion gradients (terminal ischemic depolarization) of the cortex during complete global ischemia.

Methods

As pericranial temperature was varied between 39 and 25 degrees C in normocapnic halothane-anesthetized rats, CMRG (using 14C-deoxyglucose) or the time to depolarization (using a glass microelectrode in the cortex) after a K(+)-induced cardiac arrest was measured. In other studies, CMRG and depolarization times were measured in normothermic animals (37.7 +/- 0.2 degrees C) anesthetized with high-dose pentobarbital or isoflurane (both producing burst suppression on the electroencephalogram) or in halothane-anesthetized animals whose temperatures were reduced to 27.4 +/- 0.3 degrees C. These three states were designed to produce equivalent CMRG values.

Results

As temperature was reduced from 39 to 25 degrees C, CMRG decreased from 66 to 21 microM.100 g-1.min-1 (Q10 = 2.30), and depolarization times increased from 76 to 326 s. In similarly anesthetized animals at approximately 27 degrees C, CMRG was 32 +/- 4 microM.100 g-1.min-1 (mean +/- SD), whereas in normothermic pentobarbital- and isoflurane-anesthetized rats, CMRG values were 33 +/- 3 and 37 +/- 4 microM.100 g-1.min-1, respectively (P = 0.072 by one-way analysis of variance). Despite these similar metabolic rates, the times to depolarization were markedly different: for hypothermia it was 253 +/- 29 s, for pentobarbital 109 +/- 24 s, and for isoflurane 130 +/- 28 s (P < 0.0001).

Conclusions

The time to terminal depolarization is believed to be a measure of the rate at which energy stores are depleted. In this study there was a strong correlation between hypothermic reductions in CMRG and increases in the time to depolarization. This finding supports the belief that metabolic suppression may offer some cerebral protection. However, equivalent reductions in CMRG produced by hypothermia and by anesthesia were not equivalent in their effects on membrane failure. Whether hypothermia slows energy depletion by some unique mechanism or directly retards depolarization is unknown.
A Comparison of the Effects of Hypothermia, Pentobarbital, and Isoflurane on Cerebral Energy Stores at the Time of Ischemic Depolarization
Authors: Verhaegen Marleen , Iaizzo Paul A. , Todd Michael M.
Published: November 2003

Background

In an accompanying article, we report that hypothermia (27-28 degrees C) delayed postischemic cortical depolarization longer than did large-dose pentobarbital or isoflurane anesthesia, even though preischemic cerebral metabolic rates for glucose were similar in the three groups. To examine the mechanism that may underlie these differences, we measured the cerebral concentrations of high-energy phosphates (including adenosine triphosphate [ATP] and adenosine diphosphate) in normal conditions and at the moment of depolarization.

Methods

Rats were anesthetized with 0.8% halothane/50% N2O and prepared for measurement of the cortical direct-current potential by glass microelectrodes. Animals were assigned to one of four groups: (1) halothane/nitrous oxide anesthesia, pericranial temperature approximately 38 degrees C; (2) halothane/nitrous oxide, approximately 28 degrees C; (3) halothane/nitrous oxide anesthesia with pentobarbital added to achieve electroencephalographic isoelectricity, approximately 38 degrees C; or (4) 2.4% isoflurane/50% N2O anesthesia (with electroencephalographic isoelectricity), approximately 38 degrees C. The latter three groups were chosen on the basis of earlier work showing similar cerebral metabolic rates for glucose. In a subgroup of each, circulatory arrest was induced with KCl and the brain was frozen in situ (with liquid nitrogen) at the moment of cortical depolarization. In remaining animals, the brain was frozen without any ischemia. Tissue ATP, adenosine diphosphate, adenosine monophosphate, and phosphocreatine concentrations were measured by high-performance liquid chromatography.

Results

High-energy phosphate concentrations in nonischemic brain tissue were similar in all groups (e.g., ATP concentration 2.47-2.79 mumol/g brain). With ischemia, depolarization occurred when ATP concentrations had decreased to 13-18% of normal. There were no significant differences in the concentration of any compound or in the energy charge among the groups, even though the time until depolarization was much longer in hypothermic animals (242 s) than in animals receiving large doses of anesthesia (119 and 132 s) or in normothermic halothane/nitrous oxide animals (73 s).

Conclusions

The ATP/energy charge threshold for cortical depolarization was similar in all groups despite differing temperature or anesthetic conditions. Because hypothermia increased the time until depolarization, the rate of decrease in ATP concentration must have been slower in these animals than in the two groups receiving large-dose anesthetics, despite similar preischemic cerebral metabolic rates for glucose. This finding is similar to that of earlier studies and indicates that factors other than preischemic metabolic rate are responsible for controlling energy utilization after ischemia.
Halothane Reduces Focal Ischemic Injury in the Rat When Brain Temperature Is Controlled
Authors: Warner David S. , Ludwig Paula S. , Pearlstein Robert , Brinkhoust Ann D.
Published: November 2003

Background

Previous work has demonstrated that rats anesthetized with halothane during focal cerebral ischemia have better histologic and neurologic outcome than do rats undergoing the same insult when awake. The purpose of this experiment was to determine whether this difference persists when brain temperature is held similar in halothane-anesthetized and awake experimental groups.

Methods

Two ischemia experiments were performed. In both, the middle cerebral artery was occluded for 90 min. Temperature was monitored from a radiotelemetered thermistor implanted in the cerebral cortex. Four days after ischemia, infarct volume and neurologic function were assessed. In experiment 1, brain temperature was not controlled in awake rats. Temperature in rats anesthetized with halothane, approximately 1 minimum alveolar concentration, was regulated by servomechanism by surface heating or cooling to replicate the temperature profiles generated by awake animals. To address methodologic issues regarding infarct volume analysis, a subset of nine rats was examined for the effect of the histologic staining technique and the mathematical modeling algorithms used for computation of infarct volume values. In experiment 2, the brain temperature of awake and halothane-anesthetized rats was maintained normothermic (38.0 degrees C) throughout ischemia and early recirculation.

Results

In experiment 1 no difference between groups was observed for cortical (halothane 146 +/- 95 mm3 and awake 126 +/- 108 mm3; P = 0.64) or subcortical (halothane 110 +/- 48 mm3 and awake 100 +/- 66 mm3; P = 0.66) infarct volume. Neurologic function was also similar between groups. Total infarct volume was approximately 11% greater when histologic sections were stained with hematoxylin and eosin than when they were stained with nitro blue tetrazolium, although volumes correlated closely between the two techniques (r2 = 0.996). Analysis by orthogonal or frustum projection from two-dimensional planimetric areas to three-dimensional volumes resulted in nearly identical values (r2 = 0.999). In experiment 2, halothane-anesthetized rats experienced a 46% reduction in cortical infarct volume (halothane 106 +/- 97 mm3 and awake 197 +/- 103 mm3; P = 0.03). The incidence of hemiparesis was reduced in the anesthetized group (P = 0.03).

Conclusions

When brain temperature was maintained normothermic throughout the focal ischemic insult, a neurologic and histologic protective effect for halothane anesthesia was observed. This effect of halothane was not sufficient to persist when large variations in brain temperature were allowed. Regulation of brain temperature is a critical factor in the determination of the effects of anesthetics on focal ischemic brain damage.
Nitrogen Dioxide Production during Mechanical Ventilation with Nitric Oxide in Adults
Authors: Nishimura Masaji , Hess Dean , Kacmarek Robert M. , Ritz Ray , Hurford William E.
Published: November 2003

Background

Inhaled nitric oxide (NO) may be useful in the treatment of adult respiratory distress syndrome and other diseases characterized by pulmonary hypertension and hypoxemia. NO is rapidly converted to nitrogen dioxide (NO2) in oxygen (O2) environments. We hypothesized that in patients whose lungs are mechanically ventilated and in those with a long residence time for NO in the lungs, a clinically important [NO2] may be present. We therefore determined the rate constants for NO conversion in adult mechanical ventilators and in a test lung simulating prolonged intrapulmonary residence of NO.

Methods

NO (800 ppm) was blended with nitrogen (N2), delivered to the high-pressure air inlet of a Puritan-Bennett 7200ae or Siemens Servo 900C ventilator, and used to ventilate a test lung. The ventilator settings were varied: minute ventilation (VE) from 5 to 25 l/min, inspired O2 fraction (FIO2) from 0.24 to 0.87, and [NO] from 10 to 80 ppm. The experiment was then repeated with air instead of N2 as the dilution gas. The effect of pulmonary residence time on NO2 production was examined at test lung volumes of 0.5-4.0 l, VE of 5-25 l/min, FIO2 of 0.24-0.87, and [NO] of 10-80 ppm. The inspiratory gas mixture was sampled 20 cm from the Y-piece and from within the test lung. NO and NO2 were measured by chemiluminescence. The rate constant (k) for the conversion of NO to NO2 was determined from the relation 1/[NO]t-1/[NO]o = k x [O2] x t, where t = residence time.

Results

No NO2 was detected during any trial with VE 20 or 25 l/min. With N2 dilution and the Puritan-Bennett 7200ae, NO2 (< or = 1 ppm) was detected only at a VE of 5 l/min with an FIO2 of 0.87 and [NO] > or = 70 ppm. In contrast, [NO2] values were greater with the Servo 900C ventilator than with the Puritan-Bennett 7200ae at similar settings. When NO was diluted with air, clinically important [NO2] values were measured with both ventilators at high [NO] and FIO2. Rate constants were 1.46 x 10(-9) ppm-2.min-1 when NO was mixed with N2, 1.17 x 10(-8) ppm-2.min-1 when NO was blended with air, and 1.44 x 10(-9) ppm-2.min-1 in the test lung.

Conclusions

[NO2] increased with increased FIO2 and [NO], decreased VE, blending with air, and increased lung volumes. Higher [NO2] was produced with the Servo 900C ventilator than the Puritan-Bennett 7200ae because of the greater residence time. With long intrapulmonary residence times for NO, there is a potential for NO2 production within the lungs. The rate constants determined can be used to estimate [NO2] in adult mechanical ventilation systems.