Work Group: Chair, David J. Kouba, MD, PhD, Matteo C. LoPiccolo, MD, Murad Alam, MD, Jeremy S. Bordeaux, MD, MPH, Bernard Cohen, MD, C. William Hanke, MD, Nathaniel Jellinek, MD, Howard I. Maibach, MD, Jonathan W. Tanner, MD, PhD, Neelam Vashi, MD, Kenneth G. Gross, MD, Trudy Adamson, MSN, RN, DNC, Wendy Smith Begolka, MBS, and Jose V. Moyano, PhD Toledo and Cleveland, Ohio; Detroit and Shelby, Michigan; Chicago and Schaumburg, Illinois; Baltimore, Maryland; Carmel, Indiana; East Greenwich, Rhode Island; San Francisco and San Diego, California; Philadelphia, Pennsylvania; Boston, Massachusetts; and Rochester, Minnesota

There are an increasing number and variety of dermatologic surgical procedures performed safely in the office setting. This evidence-based guideline addresses important clinical questions that arise regarding the use and safety of local anesthesia for dermatologic office-based procedures. In addition to recommendations for dermatologists, this guideline also takes into account patient preferences while optimizing their safety and quality of care. The clinical recommendations presented here are based on the best evidence available as well as expert opinion.

BACKGROUND:Providing anesthesia and managing airways in the electrophysiology suite can be challenging because of its unique setting outside of the conventional operating room. We report our experience of several cases of reported airway trauma including tongue and pharyngeal hematoma and vocal cord paralysis in this setting. METHODS:We analyzed all of the reported airway trauma cases between December 2009 and January 2011 in our cardiac electrophysiology laboratories and compared these cases with those without airway trauma. Data from 87 cases, including 16 cases with reported airway trauma (trauma group) and 71 cases without reported airway trauma from the same patient population pool at the same period (control group), were collected via review of medical records. RESULTS:Airway trauma was reported for 16 patients (0.7%) in 14 months among 2434 anesthetic cases. None of these patients had life-threatening airway obstruction. The avoidance of muscle relaxants during induction in patients with a body mass index less than 30 was found to be a significant risk factor for airway trauma (P = 0.04; odds ratio, 10; 95% confidence interval, 1.1-482). Tongue or soft tissue bite occurred in 2 cases where soft bite block was not used during cardioversion. No statistically significant difference was found between the trauma and the control groups for preprocedure anticoagulation, anticoagulation during the procedure, or reversal of heparin at the end of the procedure. CONCLUSIONS:The overall incidence of reported airway trauma was 0.7% in our study population. Tongue injury was the most common airway trauma. The cause seems to have been multifactorial; however, airway management without muscle relaxant emerged as a potential risk factor. Intubation with muscle relaxant is recommended, as is placing a soft bite block and ensuring no soft tissue is between the teeth before cardioversion.

Monitoring depth of anesthesia via the processed electroencephalogram (EEG) has been found useful in reducing the amount of anesthetic drugs, optimizing wake-up times, and, in some studies, reducing awareness. Our goal was to determine if titrating sevoflurane as the maintenance anesthetic to a depth of anesthesia monitor (SEDLine™, Masimo, CA) would shorten time to extubation in elderly patients undergoing non-cardiac surgery while on beta-adrenergic blockade. This patient population was selected because the usual cardiovascular signs of inadequate general anesthesia may be masked by beta-blocker therapy.

BACKGROUND:Patient-controlled sedation (PCS) with propofol has been advocated as a method for dealing with the narrow therapeutic window for moderate sedation, but previous studies have methodologic limitations. We hypothesized that, by using remifentanil in conjunction with propofol and using PCS in both arms of the study, we could demonstrate marked improvements in facility use compared with fentanyl plus midazolam. METHODS:Fifty patients undergoing elective colonoscopy were randomized (with concealed allocation) to midazolam/fentanyl (group MF) or propofol/remifentanil (group PR) administered via PCS. Time intervals for sedation and recovery, perceptions by patient, nurse, and gastroenterologist, and need for anesthesiologist intervention were assessed. RESULTS:Group PR patients were sedated and recovered significantly more rapidly than did group MF (P < 0.0001). In the group PR, recovery room time was actually shorter than procedure room time. Patient, nurse, and gastroenterologist perceptions were equivalent between the groups. Two patients in group PR required anesthesiologist intervention for arterial desaturation exceeding the primary safety end point. CONCLUSIONS:PCS with propofol/remifentanil yields superior facility throughput compared with midazolam/fentanyl when used in an appropriate care setting.

Xenon and dichloromethane are inhalational anesthetic agents whose binding to myoglobin has been demonstrated by X-ray crystallography. We explore the thermodynamic significance of such binding using differential scanning calorimetry, circular dichroism spectroscopy, and hydrogen-tritium exchange measurements to study the effect of these agents on myoglobin folding stability. Though specific binding of these anesthetics might be expected to stabilize myoglobin against unfolding, dichloromethane actually destabilized myoglobin at all examined concentrations of this anesthetic (15, 40, and 200 mM). On the other hand, xenon (1 atm) stabilized myoglobin. Thus, dichloromethane and xenon have opposite effects on myoglobin stability despite localization in comparably folded X-ray crystallographic structures. These results suggest a need for solution measurements to complement crystallography if the consequences of weak binding to proteins are to be appreciated.

A loss of potency as one ascends a homologous series of compounds (cutoff effect) is often used to map the dimensions of binding sites on a protein target. The implicit assumption of steric hindrance is rarely confirmed with direct binding measurements, yet other mechanisms for cutoff exist. We studied the binding and effect of a series of n-alkanols up to hexadecanol (C16) on two model proteins, BSA and myoglobin (MGB), using hydrogen-tritium exchange and light scattering. BSA binds the n-alkanols specifically and, at 1 mM total concentration, is stabilized with increasing potency up to decanol (C10), where a loss in stabilizing potency occurs. Cutoff in stabilizing potency is concentration-dependent and occurs at progressively longer n-alkanols at progressively lower total n-alkanol concentrations. Light scattering measurements of n-alkanol/BSA solutions show a smooth decline in binding stoichiometry with increasing chain length until C14-16, where it levels off at approximately 2:1 (alkanol:BSA). MGB does not bind the n-alkanols specifically and is destabilized by them with increasing potency until C10, where a loss in destabilizing potency occurs. Like BSA, MGB demonstrates a concentration-dependent cutoff point for the n-alkanols. Derivation of the number of methylenes bound at K(D) and the free energy contribution per bound methylene showed that no discontinuity existed to explain cutoff, rendering steric hindrance unlikely. The data also allow an energetic explanation for the variance of the cutoff point in various reductionist systems. Finally, these results render cutoff an untenable approach for mapping binding site sterics in the absence of complementary binding measurements, and a poor discriminator of target relevance to general anesthesia.

Inhalational anesthetic agents are known to alter protein function, but the nature of the interactions underlying these effects remains poorly understood. We have used differential scanning calorimetry to study the effects of the anesthetic agent halothane on the thermally induced unfolding transition of bovine serum albumin. We find that halothane (0.6–10 mM) stabilizes the folded state of this protein, increasing its transition midpoint temperature from 62 to 71°C. Binding of halothane to the native state of serum albumin thus outweighs any non-specific interactions between the thermally unfolded state of serum albumin and halothane in this concentration range. Based on the average enthalpy change ΔH for unfolding of 170 kcal/mol, the increase from 62 to 71°C corresponds to an additional Gibbs energy of stabilization (ΔΔG) due to halothane of more than 4 kcal/mol. Analysis of the dependence of ΔΔG on halothane concentration shows that thermal unfolding of a bovine serum albumin molecule is linked to the dissociation of about one halothane molecule at lower halothane concentrations and about six at higher halothane concentrations. Serum albumin is the first protein that has been shown to be stabilized by an inhalational anesthetic.

1. We have used differential scanning calorimetry to measure the halothane induced change in stability of five lipid-free proteins in aqueous solution. 2. The temperature at peak heat capacity (Tm) as the sample is heated provides a measure of stability. 3. Addition of halothane increases Tm for bovine and human serum albumin, but decreases Tm for hen egg white lysozyme, bovine pancreatic ribonuclease A, and horse skeletal muscle myoglobin. 4. A shift of Tm in either direction may model the action of inhaled anesthetics on relevant proteins in the central nervous system.

To understand further the weak molecular interactions between inhaled anesthetics and proteins, we studied the character and dynamic consequences of halothane binding to bovine serum albumin (BSA) and myoglobin using photoaffinity labeling and hydrogen-tritium exchange (HX). We find that halothane binds saturably and with submillimolar affinity to BSA, but either nonspecifically or with considerably lower affinity to myoglobin. Titration of halothane binding with guanidine hydrochloride suggested more protection of binding sites from solvent in BSA as compared with myoglobin. Protection factors for slowly exchanging albumin hydrogens are increased in a concentration-dependent manner by up to 27-fold with 10 mM halothane, whereas more rapidly exchanging groups of albumin hydrogens have either unaltered or decreased protection factors. Protection factors for slowly exchanging hydrogens in myoglobin are decreased by halothane, suggesting destabilization through binding to an intermediate or completely unfolded conformer. These results demonstrate the conformation dependence of halothane binding and clear dynamic consequences that correlate with the character of binding in these model proteins. Preferential binding and stabilization of different conformational states may underlie anesthetic-induced protein dysfunction, as well as provide an explanation for heterogeneity of action.

A loss of potency as one ascends a homologous series of compounds (cutoff effect) is often used to map the dimensions of binding sites on a protein target. The implicit assumption of steric hindrance is rarely confirmed with direct binding mea- surements, yet other mechanisms for cutoff exist. We studied the binding and effect of a series of n-alkanols up to hexade- canol (C16) on two model proteins, BSA and myoglobin (MGB), using hydrogen-tritium exchange and light scattering. BSA binds the n-alkanols specifically and, at 1 mM total concentra- tion, is stabilized with increasing potency up to decanol (C10), where a loss in stabilizing potency occurs. Cutoff in stabilizing potency is concentration-dependent and occurs at progres- sively longer n-alkanols at progressively lower total n-alkanol concentrations. Light scattering measurements of n-alkanol/ BSA solutions show a smooth decline in binding stoichiometry with increasing chain length until C14 -16, where it levels off at ;2;1 (alkanol;BSA). MGB does not bind the n-alkanols spe- cifically and is destabilized by them with increasing potency until C10, where a loss in destabilizing potency occurs. Like BSA, MGB demonstrates a concentration-dependent cutoff point for the n-alkanols. Derivation of the number of methylenes bound at KD and the free energy contribution per bound meth- ylene showed that no discontinuity existed to explain cutoff, rendering steric hindrance unlikely. The data also allow an energetic explanation for the variance of the cutoff point in various reductionist systems. Finally, these results render cutoff an untenable approach for mapping binding site sterics in the absence of complementary binding measurements, and a poor discriminator of target relevance to general anesthesia.

This review highlights developments from the last few years in the quest to understand the mechanism of action of inha- lational anesthetic agents. The spinal cord, not just the brain, is an important site of anesthetic action. Mutations in the gamma-aminobutyric acid (GABAA) receptor alter its anesthetic sensitivity, but this receptor cannot explain all of inhalational anesthetic action. It is still unresolved whether direct effects on proteins or indirect effects via lipids are important for inhaled anesthetic action. Recent evidence suggests that specific interactions between inhaled anesthetics and proteins replicate phenomena expected of anesthesia better than do nonspecific interactions.