Analgesia with Noninvasive electrical stimulation: challenges when finding optimal parameters of stimulation

Translate Request has too much data Parameter name: request Translate Request has too much data Parameter name: request Analgesia with Noninvasive Electrical Cortical Stimulation: Challenges to Find Optimal Parameters of Stimulation Skip to main page content

HOME CURRENT ISSUE PAST ISSUES CME SUBSCRIBE ONLINE HELP SUBMIT TO A&A ACTIVATE MY ACCOUNT Search GO Advanced Search ? User Name Password Sign In Analgesia with Noninvasive Electrical Cortical Stimulation: Challenges to Find Optimal Parameters of Stimulation Felipe Fregni, MD, PhD

From the Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts. Address correspondence and reprint requests to Felipe Fregni, MD, PhD, Spaulding Rehabilitation Hospital, 125 Nashua St., Boston, MA 02144. Address e-mail to fregni.felipe{at}mgh.harvard.edu. Acute and chronic pain are common disorders that have detrimental effects on physical and psychological health, quality of life, employment, and economic well-being.1,2 Despite the fact that pain is extensively studied, the therapeutic options available for pain are limited because of the adverse effects associated with drugs for acute pain treatment and inadequate efficacy for chronic pain treatment. Moreover, the exploding use of opioids, the most frequently prescribed medications in the United States, has been associated with increased incidence of misuse, abuse, overdoses, and deaths, creating a major public health concern.3 An unmet need for new and safe analgesic modalities has been indeed recognized at the regulatory level.

Given this scenario, a surging interest in developing noninvasive, nonpharmacological approaches to analgesia is not surprising. One of these approaches is noninvasive cortical stimulation with weak electrical currents. In this issue of Anesthesia & Analgesia, Nekhendzy et al.4 show that transcranial electrical stimulation (TES), using a combination of AC and DC currents, induces significant analgesic effects in healthy subjects, as indexed by heat and mechanical threshold. Interestingly, this study also demonstrated a significant effect with experimentally induced ultraviolet B (UVB) skin sunburns.

The first key issue is whether there is a rationale for the use of cortical stimulation in the treatment of pain. There have been several recent studies investigating the use of electrical and magnetic cortical stimulation in the treatment of chronic and acute pain.5–7 In fact, the idea of using brain stimulation to treat pain syndromes is not a new concept. A MEDLINE search using the terms “brain stimulation” and “pain,” conducted in May 2010, yielded 3349 articles dating back to the 1950s, including work from Delgado et al.8 and Melzack and Melinkoff.9 However, development of this field has been slow as compared with the development and use of drugs. There are several reasons that can explain this stunted development including lack of well-controlled studies, absent standardization of treatment paradigms and stimulation parameters (i.e., frequency, intensity and duration of stimulation, signal waveform, and electrode/coil positioning and configuration), as well as other methodological issues. This has resulted in difficulty disseminating the results among laboratories.10–13 Brain stimulation studies use different parameters of stimulation in different settings and under different conditions. Therefore, it is difficult to assess and compare results across studies. In fact, to ensure the wide acceptance of novel treatments, it is critical that mechanistic studies be conducted, and replicated, by different laboratories. This can explain the rapid development of 2 new techniques of noninvasive brain stimulation for pain modulation: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS).

The study by Nekhendzy et al. can be compared, to some extent, with current research on TMS and tDCS. In particular, this study used a technique called transcranial electrostimulation (TES). The first question then becomes: Is TES (as used in the study by Nekhendzy et al.) similar to either tDCS or TMS? Although this technique shares some key similarities with TMS and tDCS, it also has critical differences. For instance, the authors used both DC and AC current, and the DC current, in this case, inverted polarity every 10 minutes. This differs from the standard use of DC, in which the same direction of current is maintained throughout the experiment.14 Furthermore, the pulses induced by AC, when compared with pulses induced by repetitive TMS, have different characteristics; AC stimulation in this study induces a pulse of significantly less intensity. In addition, the AC current frequency used in this particular study was larger than is traditionally used in TMS. Furthermore, the current distribution field is fundamentally different. Finally, this study combined these 2 methods of electrical stimulation. It is therefore not straightforward to compare the results of TES used in the study by Nekhendzy et al. with the 2 most common techniques of noninvasive brain stimulation for the treatment of pain (TMS and tDCS).

In the current study by Nekhendzy et al.,4 20 participants, all healthy Caucasian males, were randomly assigned to receive TES 60 Hz (active treatment) and TES 100 Hz (active control) in a randomized order. Each participant received a small UVB experimental lesion on the skin of the upper thigh. Both heat and mechanical pain thresholds were measured in both normal and UVB lesion areas of skin. Measures were taken at baseline, 15 minutes after the start of TES, and 45 minutes after TES ended. TES was administered for 35 minutes per TES session. The authors demonstrated that TES at 60 Hz and 100 Hz induces a significant change in thermal and mechanical pain thresholds in the UVB lesion. Furthermore, these TES frequencies attenuated thermal pain in the normal skin during, but not after, stimulation, compared with the baseline. Finally, TES 60 Hz was found to be significantly more effective than TES 100 Hz in pain control.

There are several points that need to be discussed. The first important issue is whether currents penetrated the skull and reached the cortex. This is a key issue that has been addressed by several modeling studies. For instance, Wagner et al.15 found that although electrical currents of small intensities can be injected into the brain, the amount of current that reaches the cortex is relatively small. Another important conclusion of this study is that the peak of current density depends critically on electrode position. In addition, the currents induced in the brain by weak electrical current do not directly induce action potentials; therefore, these currents do not directly stimulate neurons but, rather, modulate their excitability. In another modeling study, which involved the entire head and additional structures such as blood, fat, and cartilage, similar results were found.16

Based on these modeling studies, 2 considerations must be made. (1) Because current distribution depends critically on electrode position, does the electrode montage in the study by Nekhendzy et al. induce a significant intracranial current? Interestingly, a previous modeling study assessed a very similar montage as in this study, in which a large anode was placed symmetrically above the eyebrows with 2 small cathodes placed over the mastoids.17 The results showed that although a significant amount of current can be injected transcranially, this value is smaller compared with the most typical montage (M1-supraorbital area and dorsolateral prefrontal cortex-supraorbital area). (2) Considering that a significant amount of current can be injected transcranially, it is vital to localize the peak of current induced to determine whether any behavioral effects are related to its intracranial stimulation.

Another important issue is the discussion of potential clinical application of this technique, as tested by Nekhendzy et al. Here, important considerations need to be made. (1) This study tested a population of healthy subjects only. Although the authors also used the model of UVB skin lesion to mimic effects of local hypersensitization, it is not possible to derive from this current study that these effects can be translated for patients with chronic pain. (2) Nekhendzy et al. showed no poststimulation analgesia/antihyperalgesia, because no effects were detected after 45 minutes of TES discontinuation. However, it also needs to be considered here that the authors tested a single session of TES, which might have only a short-term effect. With other techniques of brain stimulation, such as tDCS, it has been shown that the number of sessions is associated with duration of after-effects.18,19

Finally, a discussion of the mechanisms of action for this intervention is necessary. First, it is possible that some of the effects found in this study are related to DC stimulation. Because current was inversed every 10 minutes, it is difficult to conceive how DC could have influenced these effects. As several studies have indicated, the effects of DC are correlated with the polarity of stimulation.14,20 Thus, it is unlikely that these effects are attributable to the DC component only. As for AC stimulation, studies have shown that this type of current can induce several effects such as biochemical changes (i.e., neurotransmitter and endorphin release), interruption of ongoing cortical activity (i.e., introducing cortical noise [see review15]), and modulation of membrane threshold. In fact, repetitive extracellular high-frequency stimulation in cultured rat neurons has been shown to activate an inward sodium current, which gives rise to a weak depolarization of the cell membrane.21

The effects of cranial AC stimulation might also be attributable to a primary effect on the peripheral nervous system, which is secondarily transmitted to the central nervous system. In a previous study, the same group of authors showed that peripheral craniospinal sensory nerves have a critical role in mediating the antinociceptive action of pulsed electrical stimulation.22 In that particular study, the antinociceptive effects of stimulation were blocked with the application of local anesthetic, injected under the stimulation electrodes. Therefore, cranial AC stimulation may function via a mechanism similar to transcutaneous electrical nerve stimulation units.

The effects found in this study might have resulted from the combination, and not the addition, of the 2 components (AC and DC). Indeed, researchers of previous early studies tried to combine AC and DC currents, but with different parameters, such as the use of Lebedev current. In this method, 2 AC pulses are administered at 77.5 Hz for 3.5 to 4 milliseconds, followed by a 4-second stream of constant DC.14 There are some studies showing significant behavioral effects using this particular current; however, there is a lack of mechanistic studies to fully confirm these behavioral effects.

The well-conducted study by Nekhendzy et al.4 adds important data for the development of noninvasive cortical stimulation as an analgesic method. Although this analgesic effect still needs to be confirmed in patients with acute and/or chronic pain, this is the first step for such development. Further studies are needed to investigate mechanisms of action and, more importantly, determine optimal parameters of stimulation by not only testing different parameters, but also by comparing with more established techniques of noninvasive brain stimulation such as TMS and tDCS.

 Next Section AUTHOR CONTRIBUTIONS Felipe Fregni wrote the manuscript and approved the final manuscript.

Previous SectionNext Section Footnotes Supported by the National Institutes of Health (NIH 7R21DK081773).

Disclosure: The author reports no conflicts of interest.

Dr. Fregni's current affiliation is Department of Physical Medicine and Rehabilitation and Department of Neurology, Harvard Medical School, Boston, MA.

Accepted July 15, 2010. Copyright ? 2010 International Anesthesia Research Society Previous Section  REFERENCES 1.? van Hanswijck de Jonge P, Lloyd A, Horsfall L, Tan R, O'Dwyer PJ . The measurement of chronic pain and health-related quality of life following inguinal hernia repair: a review of the literature. Hernia 2008;12:561–9 Medline 2.? Jensen MP, Chodroff MJ, Dworkin RH . The impact of neuropathic pain on health-related quality of life: review and implications. Neurology 2007;68:1178–82 Abstract/FREE Full Text 3.? McLellan AT, Turner BJ . Chronic noncancer pain management and opioid overdose: time to change prescribing practices. Ann Intern Med 2010;152:123–4 FREE Full Text 4.? Nekhendzy V, Lemmens HJ, Tingle M, Nekhendzy M, Angst MS . The analgesic and antihyperalgesic effects of transcranial electrostimulation with combined direct and alternating current in healthy volunteers. Anesth Analg 2010;111:1301–7 Abstract/FREE Full Text 5.? Fregni F, Freedman S, Pascual-Leone A . Recent advances in the treatment of chronic pain with non-invasive brain stimulation techniques. Lancet Neurol 2007;6:188–91 Medline 6.? Lefaucheur JP . Use of repetitive transcranial magnetic stimulation in pain relief. Expert Rev Neurother 2008;8:799–808 CrossRefMedline 7.? Borckardt JJ, Weinstein M, Reeves ST, Kozel FA, Nahas Z, Smith AR, Byrne TK, Morgan K, George MS . Postoperative left prefrontal repetitive transcranial magnetic stimulation reduces patient-controlled analgesia use. Anesthesiology 2006;105: 557–62 Medline 8.? Delgado JM, Roberts WW, Miller NE . Learning motivated by electrical stimulation of the brain. Am J Physiol 1954;179: 587–93 FREE Full Text 9.? Melzack R, Melinkoff DF . Analgesia produced by brain stimulation: evidence of a prolonged onset period. Exp Neurol 1974;43:369–74 CrossRefMedline 10.? Edelmuth RC, Nitsche MA, Battistella L, Fregni F . Why do some promising brain-stimulation devices fail the next steps of clinical development? Expert Rev Med Devices 2010;7:67–97 Medline 11.? Kroeling P, Gross AR, Goldsmith CH . A Cochrane review of electrotherapy for mechanical neck disorders. Spine (Phila Pa 1976) 2005;30:E641–8 12.? Alling FA, Johnson BD, Elmoghazy E . Cranial electrostimulation (CES) use in the detoxification of opiate-dependent patients. J Subst Abuse Treat 1990;7:173–80 CrossRefMedline 13.? Lima MC, Fregni F . Motor cortex stimulation for chronic pain: systematic review and meta-analysis of the literature. Neurology 2008;70:2329–37 Abstract/FREE Full Text 14.? Zaghi S, Acar M, Hultgren B, Boggio PS, Fregni F . Noninvasive brain stimulation with low-intensity electrical currents: putative mechanisms of action for direct and alternating current stimulation. Neuroscientist 2010;16:285–307 Abstract/FREE Full Text 15.? Wagner T, Fregni F, Fecteau S, Grodzinsky A, Zahn M, Pascual-Leone A . Transcranial direct current stimulation: a computer-based human model study. Neuroimage 2007;35: 1113–24 CrossRefMedline 16.? Sadleir RJ, Vannorsdall TD, Schretlen DJ, Gordon B . Transcranial direct current stimulation (tDCS) in a realistic head model. Neuroimage 2010;51:1310–8 CrossRefMedline 17.? Miranda PC, Lomarev M, Hallett M . Modeling the current distribution during transcranial direct current stimulation. Clin Neurophysiol 2006;117:1623–9 CrossRefMedline 18.? Boggio PS, Nunes A, Rigonatti SP, Nitsche MA, Pascual-Leone A, Fregni F . Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients. Restor Neurol Neurosci 2007;25:123–9 Medline 19.? Fregni F, Boggio PS, Lima MC, Ferreira MJ, Wagner T, Rigonatti SP, Castro AW, Souza DR, Riberto M, Freedman SD, Nitsche MA, Pascual-Leone A . A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. Pain 2006; 122:197–209 CrossRefMedline 20.? Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, Paulus W, Hummel F, Boggio PS, Fregni F, Pascual-Leone A . Transcranial direct current stimulation: state of the art 2008. Brain Stimul 2008;1:206–23 CrossRefMedline 21.? Schoen I, Fromherz P . Extracellular stimulation of mammalian neurons through repetitive activation of Na+ channels by weak capacitive currents on a silicon chip. J Neurophysiol 2008;100:346–57 Abstract/FREE Full Text 22.? Nekhendzy V, Davies MF, Lemmens HJ, Maze M . The role of the craniospinal nerves in mediating the antinociceptive effect of transcranial electrostimulation in the rat. Anesth Analg 2006;102:1775–80 Abstract/FREE Full Text ? Previous | Next Article ?Table of Contents This Article doi: 10.1213/?ANE.0b013e3181f4dcdb A & A November 2010 vol. 111 no. 5 1083-1085 ? Full Text Full Text (PDF) Classifications Editorial Services Email this article to a colleague Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in PubMed Download to citation manager Request Permissions Citing Articles Load citing article information Citing articles via Google Scholar Google Scholar Articles by Fregni, F. Search for related content PubMed PubMed citation Articles by Fregni, F. Related Content Mechanisms Pain Medicine Pain Load related web page information Navigate This Article Top AUTHOR CONTRIBUTIONS Footnotes REFERENCES Current Issue August 2011, 113 (2) Alert me to new issues of A & A Join the IARS About A&A Mission Editorial Board For Authors For Reviewers Cover Art Sign up Sign up for eTOCs Sign up for RSS feeds Browse by Topic Permissions and Copyright Press Room OpenAnesthesia Advertise in A&A Career Center Most Read Special Article: 2010 Anesthesia & Analgesia Guide for Authors: 2009-2010 Editorial Board, Anesthesia & Analgesia Hand Contamination of Anesthesia Providers Is an Important Risk Factor for Intraoperative Bacterial Transmission Postoperative Sore Throat: More Answers Than Questions Nitrous Oxide and Long-Term Morbidity and Mortality in the ENIGMA Trial Surgical Site Infections and the Anesthesia Professionals' Microbiome: We've All Been Slimed! Now What Are We Going to Do About It? ? View all Most Read articles Cited ASE/SCA Guidelines for Performing a Comprehensive Intraoperative Multiplane Transesophageal Echocardiography Examination: Recommendations of the American Society of Echocardiography Council for Intraoperative Echocardiography and the Society of Cardiovascular Anesthesiologists Task Force for Certification in Perioperative Transesophageal Echocardiography The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials Cerebral Autoregulation and Flow/Metabolism Coupling during Cardiopulmonary Bypass: The Influence of Paco2 Consensus Guidelines for Managing Postoperative Nausea and Vomiting A Postanesthetic Recovery Score ? View all Most Cited articles Copyright ? 2011 by the International Anesthesia Research Society

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Antisepsis in conjunction with antibiotics: follow in the footsteps of John Snow and Joseph Lister

Translate Request has too much data Parameter name: request Translate Request has too much data Parameter name: request Antisepsis in the Time of Antibiotics: Following in the Footsteps of John Snow and Joseph Lister Skip to main page content

HOME CURRENT ISSUE PAST ISSUES CME SUBSCRIBE ONLINE HELP SUBMIT TO A&A ACTIVATE MY ACCOUNT Search GO Advanced Search ? User Name Password Sign In Antisepsis in the Time of Antibiotics: Following in the Footsteps of John Snow and Joseph Lister Markus W. Hollmann, MD* and Raymond C. Roy, MD, PhD?

From the *Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and ?Department of Anesthesiology, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina. Address correspondence and reprint requests to Raymond C. Roy, MD, PhD, Department of Anesthesiology, Wake Forest University Baptist Medical Center, Medical Center Blvd., Winston-Salem, NC 27157-1009. Address e-mail to rroy{at}wfubmc.edu. If John Snow, a founding father of both anesthesiology and epidemiology, were alive today, undoubtedly he would attack the problem of health care–associated infections (HCAIs) as doggedly as he approached the 1854 cholera epidemic in London.1 Although Snow did not know that Vibrio cholerae was the causative organism, he clearly demonstrated that cholera was communicated by drinking contaminated water from the Broad Street pump. Conversely, in the case of HCAIs associated with surgery, the causative organisms are readily determined, yet the source and mechanism of transmission are frequently unclear. Following in the footsteps of Snow are Koff, Loftus, and their Dartmouth colleagues. They are exploring whether anesthesia providers are the source, or vectors for the transmission, of bacteria that cause surgical site infections (SSIs). In earlier publications, they documented transmission of pathogenic bacteria to the anesthesia operating room work area and established an association between contamination of this area and contamination of IV stopcocks, between contaminated stopcocks and nosocomial infections, and between contamination, nosocomial infection, and hand hygiene by anesthesia providers.2,3

If Joseph Lister, founding father of antiseptic surgery, were alive today, he would be pleased with the low SSI rate today compared with 1867.4 Undoubtedly he would have applied his antiseptic protocols, including carbolic acid, not only to the surgical field and instruments but also to the anesthesia work area and equipment if they had existed in his day. However, in his era, there were no laryngoscopes, bronchoscopes, or endotracheal tubes to pass through bacteria-rich oral and nasal cavities, no spinal or epidural needles or central venous catheters to disrupt the integument, and no anesthesia machines to contaminate. Following in the footsteps of Lister, the Dartmouth group demonstrated that improved hand hygiene by anesthesia providers reduced HCAIs at their institution in their study patients.3 In this issue of Anesthesia & Analgesia, this group goes on to document anesthesia work area and IV stopcock contamination by anesthesia providers in and between operating rooms and between the first and second case in the same operating room, despite application of hand hygiene and anesthesia work area antisepsis protocols typical in modern operating rooms.5

Most anesthesiologists and their quality of care arbiters currently believe that the major contribution of the anesthesia team to the reduction of HCAIs relates to antimicrobial prophylaxis. Unfortunately, approximately 5% of surgical patients continue to experience SSIs despite timely administration of the appropriate antibiotic. In one recent study, intensifying the already rigorous intraoperative antisepsis protocol for surgeons did not reduce SSIs.6 In another, surgical glove perforation did not increase SSIs in patients who received antibiotics.7 If we have reached a plateau in our attempts to lower the SSI rate because we have gone as far as we reasonably can with surgical antisepsis and antimicrobial prophylaxis, then the remaining targets are the patient and the anesthesia provider. Does the work of Koff, Loftus, and others suggest that anesthesia providers have become the typhoid Marys and Johns of the 21st century?8,9 We think these monikers are premature until 4 issues are addressed and resolved: contamination as a surrogate marker versus cause of infection, reproducibility of data, completeness of the data, and consequences of proposed changes in protocols.

Contamination of surgical gloves, instruments, and anesthesia equipment has been demonstrated many times as a function of time from the last cleansing or opening to air and exposure to activity by health care personnel or patients.10–12 However, contamination is not equivalent to infection. It is reasonable to assume that the level of contamination is a reliable marker for the effectiveness of cleaning protocols and that above a certain level contamination may spread to sites where bacteria can be introduced or reintroduced to the patient, such as stopcocks.2 If the bacteria causing the SSI comes from colonizing sites within the patient's own microbiome, as is currently believed to be occurring most frequently,13 and the source of the bacteria contaminating the anesthesia site is also the patient, then the level of contamination is a reasonable surrogate marker for HCAI. In this situation, however, it is difficult to understand how more frequent handwashing and more effective decontamination will reduce the incidence of SSI, unless the primary route of bacterial migration is from the patient to the surgical site via the anesthesia field, stopcock in the IV line, and the blood. Similarly, decontamination of the anesthesia work area seems unlikely to reduce the incidence of postoperative pneumonia if the causative bacteria are transmitted from the patient's own oropharynx or nasopharynx by the endotracheal tube.14 Better patient preparation may be where efforts are best focused. Identifying patients who are nasal carriers of Staphylococcus aureus, treating their infection with antibiotic ointment and antiseptic wash preoperatively, and providing antiseptic mouthwash to intubated patients have proven to be effective measures to reduce HCAI.15,16

If the origin of the bacterial contamination of anesthesia equipment and IV stopcocks is the anesthesia provider, and the bacteria causing the SSI is identical to that carried by the anesthesia provider, then the level of contamination may identify him or her as the cause of SSI. Koff and Loftus et al. have documented this potential but not the actual occurrence. However, an editorial in this issue of the journal provides 2 examples whereby a specific anesthesiologist and a surgeon were clearly identified either as the cause of or the vector for several SSIs.17 The studies by Loftus et al. need to be reproduced at other institutions to confirm their observations of a reduction of HCAIs from 17.2% to 3.8%.3 If similar results are obtained, then the contribution of bacteria from the microbiome of anesthesia providers has been significantly underestimated as a cause of HCAI. A logical next step would then be to collect contamination and SSI data for each anesthesia provider. If an association is established, most likely he or she is shedding bacteria above the norm because of a treatable condition, such as eczema, an upper respiratory infection superimposed on nasal colonization of S aureus, or carbunculosis.17

Two major defense mechanisms for skeptics are challenging the data or declaring the cure as worse than the disease. But even supporters of improved hand hygiene call for better data in 2 areas. One is that many HCAIs manifest after the patient has left the hospital or outpatient surgery center and are frequently not included in outcomes data.18,19 Thus, the current data underestimate the problem. Finally, we must remember we are trying to eliminate SSIs. Measures that reduce contamination must also reduce the SSI rate. Instituting policies and procedures without subjecting them to evidence-based scrutiny may increase the cost and decrease the convenience of providing care, or even worse, increase the infection rate.20 Two examples support the need for testing protocol changes for effectiveness. First, when a needleless IV access device replaced a conventional needle access device, HCAIs increased.21 Second, protocol-driven handwashing and glove wearing did not reduce bacterial colonization and contamination in nurses with dermatitis.22 This is not an argument against washing hands or wearing gloves, but evidence that we need to develop multiple strategies to reduce contamination and infection.

We have not yet found the solution to the problem of HCAI in general or SSI in particular. It needs more attention from the anesthesia community than it has historically provided despite the interest of our founding fathers. At the very minimum we should do 3 things: (1) determine the effectiveness of our local anesthesia work area decontamination protocols, (2) continue to administer the proper antibiotic in a timely manner, and (3) continue to wash our hands between cases. However, we also plead that the study by Koff et al.3 demonstrating decreased SSIs with increased handwashing by anesthesia providers be repeated at several other institutions.

 Next Section AUTHOR CONTRIBUTIONS Both authors helped design the study, conduct the study, analyze the data, and write the manuscript. Both authors approved the final manuscript.

Previous SectionNext Section Footnotes Supported by department funds.

The authors report no conflicts of interest.

Accepted August 5, 2010. Copyright ? 2010 International Anesthesia Research Society Previous Section  REFERENCES 1.? Paneth N . Assessing the contributions of John Snow to epidemiology 150 years after removal of the Broad Street pump handle. Epidemiology 2004;15:514–6 CrossRefMedline 2.? Loftus RW, Koff MD, Burchman CC, Schwartzman JD, Thorum V, Read ME, Wood TA, Beach ML . Transmission of pathogenic bacterial organisms in the anesthesia work area. Anesthesiology 2008;109:399–407 Medline 3.? Koff MD, Loftus RW, Burchman CC, Schwartzman JD, Read ME, Henry ES, Beach ML . Reduction in intraoperative bacterial contamination of peripheral intravenous tubing through use of a novel device. Anesthesiology 2009;110:978–85 Medline 4.? Lister BJ . The classic: on the antiseptic principle in the practice of surgery. 1867. Clin Orthop Relat Res 2010;468:2012–6 Medline 5.? Loftus RW, Muffly MK, Koff MD, Brown JR, Corwin HL, Surgenor SD, Kirkland KB, Beach ML, Yeager MP . Hand contamination of anesthesia providers is an important risk factor for intraoperative bacterial transmission. Anesth Analg 2011;112:98–105 Abstract/FREE Full Text 6.? Beldi G, Bisch-Knaden S, Banz V, M?hlemann K, Candinas D . Impact of intraoperative behavior on surgical site infections. Am J Surg 2009;198:157–62 Medline 7.? Misteli H, Weber WP, Reck S, Rosenthal R, Zwahlen M, Fueglistaler P, Bolli MK, Oertli D, Widmer AF, Marti WR . Surgical glove perforation and the risk of surgical site infection. Arch Surg 2009;144:553–8 Abstract/FREE Full Text 8.? Hasian MA . Power, medical knowledge, and the rhetorical invention of “Typhoid Mary”. J Med Humanit 2000;21:123–39 Medline 9.? Hopf HW, Rollins MD . Reducing perioperative infection is as simple as washing your hands. Anesthesiology 2009;110:959–60 Medline 10.? S?Rensen P, Ejlertsen T, Aaen D, Poulsen K . Bacterial contamination of surgeons gloves during shunt insertion: a pilot study. Br J Neurosurg 2008;22:675–7 CrossRefMedline 11.? Call TR, Auerbach FJ, Riddell SW, Kiska D, Thongrod SC, Tham SW, Nussmeier NA . Nosocomial contamination of laryngoscope handles: challenging current guidelines. Anesth Analg 2009;109:479–83 Abstract/FREE Full Text 12.? Williams D, Dingley J, Jones C, Berry N . Contamination of laryngoscope handles. J Hosp Infect 2010;74:123–8 Medline 13.? Owens CD, Stoessel K . Surgical site infections: epidemiology, microbiology and prevention. J Hosp Infect 2008;70:3–10 CrossRefMedline 14.? Jacobs R, Wiener-Kronish J . Endotracheal tubes: the conduit for oral and microbial communities to the lungs. Anesthesiology 2006;104:224–5 Medline 15.? Bode LGM, Kluytuans AJW, Wertheim HFL, Bogaers D, Vandenbroucke-Grauls MJE, Roosendall R, Troelstra A, Box ATA, Voss A, van der Tweel I, van Belkum A, Verbrugh HA, Voss MC . Preventing surgical-site infections in nasal carriers of Staphylococcus aureus. N Engl J Med 2010;362:9–17 CrossRefMedline 16.? Munro CL, Grap MJ, Jones DJ, McClish DK, Sessler CN . Chlorhexidine, toothbrushing, and preventing ventilator-associated pneumonia in critically ill adults. Am J Crit Care 2009;18:428–38 Abstract/FREE Full Text 17.? Roy RC, Brull SJ, Eichhorn JH . Surgical site infections and the anesthesia professionals' microbiome: we've all been slimed! Now what are we going to do about it? Anesth Analg 2011;112:4–7 FREE Full Text 18.? Fern?ndez-Ayala M, Nan DN, Fari?as-?lverez C, Revuelta JM, Gonz?lez-Mac?as J, Fari?as MC . Surgical site infection during hospitalization and after discharge in patients who have undergone cardiac surgery. Infect Control Hosp Epidemiol 2006;27:85–8 CrossRefMedline 19.? Leaper DJ . Risk factors and epidemiology of surgical site infections. Surg Infect (Larchmt) 2010;11:1–5 Medline 20.? Dancer SJ . Pants, policies and paranoia…. J Hosp Infect 2010;74:10–15 Medline 21.? Toscano CM, Bell M, Zukerman C, Shelton W, Novicki TJ, Nichols WG, Corey L, Jarvis WR . Gram-negative bloodstream infections in hematopoietic cell transplant patients: the roles of needleless device use, bathing practices, and catheter care. Am J Infect Control 2009;37:327–34 Medline 22.? Borges LFA, Silva BL, Filho PPG, Gerais M . Hand washing: changes in skin flora. Am J Infect Control 2007;35:417–20 Medline ? Previous | Next Article ?Table of Contents This Article doi: 10.1213/?ANE.0b013e3181fa354e A & A January 2011 vol. 112 no. 1 1-3 ? Full Text Full Text (PDF) Classifications Editorial Services Email this article to a colleague Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in PubMed Download to citation manager Request Permissions Citing Articles Load citing article information Citing articles via Google Scholar Google Scholar Articles by Hollmann, M. W. Articles by Roy, R. C. Search for related content PubMed PubMed citation Articles by Hollmann, M. W. Articles by Roy, R. C. Related Content Economics and Health Care Research Complications Patient Safety Load related web page information Navigate This Article Top AUTHOR CONTRIBUTIONS Footnotes REFERENCES Current Issue August 2011, 113 (2) Alert me to new issues of A & A Join the IARS About A&A Mission Editorial Board For Authors For Reviewers Cover Art Sign up Sign up for eTOCs Sign up for RSS feeds Browse by Topic Permissions and Copyright Press Room OpenAnesthesia Advertise in A&A Career Center Most Read Special Article: 2010 Anesthesia & Analgesia Guide for Authors: 2009-2010 Editorial Board, Anesthesia & Analgesia Hand Contamination of Anesthesia Providers Is an Important Risk Factor for Intraoperative Bacterial Transmission Postoperative Sore Throat: More Answers Than Questions Nitrous Oxide and Long-Term Morbidity and Mortality in the ENIGMA Trial Surgical Site Infections and the Anesthesia Professionals' Microbiome: We've All Been Slimed! Now What Are We Going to Do About It? ? View all Most Read articles Cited ASE/SCA Guidelines for Performing a Comprehensive Intraoperative Multiplane Transesophageal Echocardiography Examination: Recommendations of the American Society of Echocardiography Council for Intraoperative Echocardiography and the Society of Cardiovascular Anesthesiologists Task Force for Certification in Perioperative Transesophageal Echocardiography The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials Cerebral Autoregulation and Flow/Metabolism Coupling during Cardiopulmonary Bypass: The Influence of Paco2 Consensus Guidelines for Managing Postoperative Nausea and Vomiting A Postanesthetic Recovery Score ? View all Most Cited articles Copyright ? 2011 by the International Anesthesia Research Society

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Review article: any antiplatelet drugs: a review of its Pharmacology and management during perioperative period

Any antiplatelet drugs: a review of its Pharmacology and management during perioperative period Skip to main page content home current query previous queries CME subscribe ONLINE using send to (A) and (A) activate my account search go advanced search? user name password characters in Antiplatelet drugs: A review of their Pharmacology and management in the perioperative Period of Richard Hall, MD, FRCPC, FCCP * and c. David Mazer, MD, FRCPC ? ?

From the *Departments of Anesthesia, Medicine, Surgery, and Pharmacology, Dalhousie University/Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia; ?Keenan Research Center/Li Ka Shing Knowledge Translation Institute, Saint Michael's Hospital, Toronto; and ?Departments of Anesthesia and Physiology, University of Toronto, Toronto, Ontario, Canada. Address correspondence and reprint requests to C. David Mazer, MD, FRCPC, Department of Anesthesia, St. Michael's Hospital, 30 Bond St., Toronto, ON M5B 1W8, Canada. Address e-mail to mazerd{at}smh.ca. Abstract In the normal course of the delivery of care, anesthesiologists encounter many patients who are receiving drugs that affect platelet function as a fundamental part of primary and secondary management of atherosclerotic thrombotic disease. There are several antiplatelet drugs available for use in clinical practice and several under investigation. Aspirin and clopidogrel (alone and in combination) have been the most studied and have the most favorable risk-benefit profiles of drugs currently available. Prasugrel was recently approved for patients with acute coronary syndrome undergoing percutaneous interventions. Other drugs such as dipyridamole and cilostazol have not been as extensively investigated. There are several newer investigational drugs such as cangrelor and ticagrelor, but whether they confer significant additional benefits remains to be established. Management of patients who are receiving antiplatelet drugs during the perioperative period requires an understanding of the underlying pathology and rationale for their administration, pharmacology and pharmacokinetics, and drug interactions. Furthermore, the risk and benefit assessment of discontinuing or continuing these drugs should be made bearing in mind the proposed surgery and its inherent risk for bleeding complications as well as decisions relating to appropriate use of general or some form of regional anesthesia. In general, the safest approach to prevent thrombosis seems to be continuation of these drugs throughout the perioperative period except where concerns about perioperative bleeding outweigh those associated with the development of thrombotic occlusion. Knowledge of the pharmacodynamics and pharmacokinetics of antiplatelet drugs may allow practitioners to anticipate difficulties associated with drug withdrawal and administration in the perioperative period including the potential for drug interactions. Footnotes Conflict of Interest: See Disclosures at the end of the article. Accepted October 1, 2010. Copyright ? 2011 International Anesthesia Research Society ? Previous | Next Article ?Table of Contents This Article Published online before print January 6, 2011, doi: 10.1213/?ANE.0b013e318203f38d A & A February 2011 vol. 112 no. 2 292-318 ? Abstract Full Text Full Text (PDF) CME Classifications Series: Review Article Cardiovascular Anesthesiology Services Email this article to a colleague Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in PubMed Download to citation manager Request Permissions Citing Articles Load citing article information Google Scholar Articles by Hall, R. Articles by Mazer, C. D. PubMed PubMed citation Articles by Hall, R. Articles by Mazer, C. D. Related Content Cardiovascular Blood Coagulation Pharmacology Load related web page information Current Issue July 2011, 113 (1) Alert me to new issues of A & A Join the IARS About A&A Mission Editorial Board For Authors For Reviewers Cover Art Sign up Sign up for eTOCs Sign up for RSS feeds Browse by Topic Permissions and Copyright Press Room OpenAnesthesia Advertise in A&A Career Center Most Read Special Article: 2010 Anesthesia & Analgesia Guide for Authors: 2009-2010 Editorial Board, Anesthesia & Analgesia Hand Contamination of Anesthesia Providers Is an Important Risk Factor for Intraoperative Bacterial Transmission Postoperative Sore Throat: More Answers Than Questions Nitrous Oxide and Long-Term Morbidity and Mortality in the ENIGMA Trial Surgical Site Infections and the Anesthesia Professionals' Microbiome: We've All Been Slimed! Now What Are We Going to Do About It? ? View all Most Read articles Cited ASE/SCA Guidelines for Performing a Comprehensive Intraoperative Multiplane Transesophageal Echocardiography Examination: Recommendations of the American Society of Echocardiography Council for Intraoperative Echocardiography and the Society of Cardiovascular Anesthesiologists Task Force for Certification in Perioperative Transesophageal Echocardiography The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials Consensus Guidelines for Managing Postoperative Nausea and Vomiting Cerebral Autoregulation and Flow/Metabolism Coupling during Cardiopulmonary Bypass: The Influence of Paco2 A Postanesthetic Recovery Score ? View all Most Cited articles Copyright ? 2011 by the International Anesthesia Research Society Print ISSN: 0003-2999 Online ISSN: 1526-7598

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Global Warming Potential of mass Anesthetics: application to clinical use

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HOME CURRENT ISSUE PAST ISSUES CME SUBSCRIBE ONLINE HELP SUBMIT TO A&A ACTIVATE MY ACCOUNT Search GO Advanced Search ? User Name Password Sign In Global Warming Potential of Inhaled Anesthetics: Application to Clinical Use Susan M. Ryan, MD, PhD* and Claus J. Nielsen, CSc?

From the *Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California; and ?Department of Chemistry, Centre for Theoretical and Computational Chemistry, University of Oslo, Oslo, Norway. Address correspondence to Susan M. Ryan, MD, PhD, 505 Parnassus Ave., Box 0648, University of California, San Francisco, San Francisco, CA 94143. Address e-mail to ryans{at}anesthesia.ucsf.edu. Abstract BACKGROUND: Inhaled anesthetics are recognized greenhouse gases. Calculating their relative impact during common clinical usage will allow comparison to each other and to carbon dioxide emissions in general.

METHODS: We determined infrared absorption cross-sections for sevoflurane and isoflurane. Twenty-year global warming potential (GWP20) values for desflurane, sevoflurane, and isoflurane were then calculated using the present and previously published infrared results, and best estimate atmospheric lifetimes were determined. The total quantity of each anesthetic used in 1 minimal alveolar concentration (MAC)-hour was then multiplied by the calculated GWP20 for that anesthetic, and expressed as “carbon dioxide equivalent” (CDE20) in grams. Common fresh gas flows and carrier gases, both air/oxygen and nitrous oxide (N2O)/oxygen, were considered in the calculations to allow these examples to represent common clinical use of inhaled anesthetics.

RESULTS: GWP20 values for the inhaled anesthetics were: sevoflurane 349, isoflurane 1401, and desflurane 3714. CDE20 values for 1 MAC-hour at 2 L fresh gas flow were: sevoflurane 6980 g, isoflurane 15,551 g, and desflurane 187,186 g. Comparison among these anesthetics produced a ratio of sevoflurane 1, isoflurane 2.2, and desflurane 26.8. When 60% N2O/40% oxygen replaced air/oxygen as a carrier gas combination, and inhaled anesthetic delivery was adjusted to deliver 1 MAC-hour of anesthetic, sevoflurane CDE20 values were 5.9 times higher with N2O than when carried with air/O2, isoflurane values were 2.9 times higher, and desflurane values were 0.4 times lower. On a 100-year time horizon with 60% N2O, the sevoflurane CDE100 values were 19 times higher than when carried in air/O2, isoflurane values were 9 times higher, and desflurane values were equal with and without N2O.

CONCLUSIONS: Under comparable and common clinical conditions, desflurane has a greater potential impact on global warming than either isoflurane or sevoflurane. N2O alone produces a sizable greenhouse gas contribution relative to sevoflurane or isoflurane. Additionally, 60% N2O combined with potent inhaled anesthetics to deliver 1 MAC of anesthetic substantially increases the environmental impact of sevoflurane and isoflurane, and decreases that of desflurane. N2O is destructive to the ozone layer as well as possessing GWP; it continues to have impact over a longer timeframe, and may not be an environmentally sound tradeoff for desflurane. From our calculations, avoiding N2O and unnecessarily high fresh gas flow rates can reduce the environmental impact of inhaled anesthetics.

Footnotes Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.anesthesia-analgesia.org).

Disclosure: The authors report no conflicts of interest.

Reprints will not be available from the author.

Copyright ? 2010 International Anesthesia Research Society ? Previous | Next Article ?Table of Contents This Article Published online before print June 2, 2010, doi: 10.1213/?ANE.0b013e3181e058d7 A & A July 2010 vol. 111 no. 1 92-98 ? Abstract Full Text Full Text (PDF) Classifications Anesthetic Pharmacology Services Email this article to a colleague Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in PubMed Download to citation manager Request Permissions Citing Articles Load citing article information Citing articles via Google Scholar Google Scholar Articles by Ryan, S. M. Articles by Nielsen, C. J. Search for related content PubMed PubMed citation Articles by Ryan, S. M. Articles by Nielsen, C. J. Related Content Economics and Health Care Research Mechanisms Ethics Pharmacology Load related web page information Current Issue July 2011, 113 (1) Alert me to new issues of A & A Join the IARS About A&A Mission Editorial Board For Authors For Reviewers Cover Art Sign up Sign up for eTOCs Sign up for RSS feeds Browse by Topic Permissions and Copyright Press Room OpenAnesthesia Advertise in A&A Career Center Most Read Special Article: 2010 Anesthesia & Analgesia Guide for Authors: 2009-2010 Editorial Board, Anesthesia & Analgesia Hand Contamination of Anesthesia Providers Is an Important Risk Factor for Intraoperative Bacterial Transmission Postoperative Sore Throat: More Answers Than Questions Nitrous Oxide and Long-Term Morbidity and Mortality in the ENIGMA Trial Surgical Site Infections and the Anesthesia Professionals' Microbiome: We've All Been Slimed! Now What Are We Going to Do About It? ? View all Most Read articles Cited ASE/SCA Guidelines for Performing a Comprehensive Intraoperative Multiplane Transesophageal Echocardiography Examination: Recommendations of the American Society of Echocardiography Council for Intraoperative Echocardiography and the Society of Cardiovascular Anesthesiologists Task Force for Certification in Perioperative Transesophageal Echocardiography The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials Consensus Guidelines for Managing Postoperative Nausea and Vomiting Cerebral Autoregulation and Flow/Metabolism Coupling during Cardiopulmonary Bypass: The Influence of Paco2 A Postanesthetic Recovery Score ? View all Most Cited articles Copyright ? 2011 by the International Anesthesia Research Society

Print ISSN: 0003-2999 Online ISSN: 1526-7598

View the original article here