Postoperative mortality in children after 101,885 anesthesia at a tertiary paediatric hospital

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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 Postoperative Mortality in Children After 101,885 Anesthetics at a Tertiary Pediatric Hospital Benjamin F. van der Griend, MBBS, BMedSc, FANZCA*, Nichole A. Lister, BA, BSc(Hons), PhD?, Ian M. McKenzie, MBBS, DipRACOG, FANZCA?, Nick Martin, MBBS, FRCA, FANZCA?, Philip G. Ragg, MBBS, FFARACS, FANZCA?, Suzette J. Sheppard, BSc(Hons)? and Andrew J. Davidson, MBBS, MD, FANZCA?

From *Christchurch Hospital, Christchurch, New Zealand and ? Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia. Address correspondence to Benjamin F. van der Griend, MBBS, BMedSc, FANZCA, Christchurch Hospital, Riccarton Avenue, Private Bag 4710, New Zealand. Address e-mail to ben{at}vandergriend.com. Abstract BACKGROUND: Mortality is a basic measure for quality and safety in anesthesia. There are few anesthesia-related mortality data available for pediatric practice. Our objective for this study was to determine the incidence of 24-hour and 30-day mortality after anesthesia and to determine the incidence and nature of anesthesia-related mortality in pediatric practice at a large tertiary institution.

METHODS: Children ?18 years old who had an anesthetic between January 1, 2003, and August 30, 2008, at the Royal Children's Hospital, Melbourne, Australia, were included for this study. Data were analyzed by merging a database for every anesthetic performed with an accurate electronic record of mortality of children who had ever been a Royal Children's Hospital patient. Cases of children dying within 30 days and 24 hours of an anesthetic were identified and the patient history and anesthetic record examined. Anesthesia-related death was defined as those cases whereby a panel of 3 senior anesthesiologists all agreed that anesthesia or factors under the control of the anesthesiologist more likely than not influenced the timing of death.

RESULTS: During this 68-month period, 101,885 anesthetics were administered to 56,263 children. The overall 24-hour mortality from any cause after anesthesia was 13.4 per 10,000 anesthetics delivered and 30-day mortality was 34.5 per 10,000 anesthetics delivered. The incidence of death was highest in children ?30 days old. Patients undergoing cardiac surgery had a higher incidence of 24-hour and 30-day mortality than did those undergoing noncardiac surgery. From 101,885 anesthetics there were 10 anesthesia-related deaths. The incidence of anesthesia-related death was 1 in 10,188 or 0.98 cases per 10,000 anesthetics performed (95%confidence interval, 0.5 to 1.8). In all 10 cases, preexisting medical conditions were identified as being a significant factor in the patient's death. Five of these cases (50%) involved children with pulmonary hypertension.

CONCLUSIONS: Anesthesia-related mortality is higher in children with heart disease and in particular those with pulmonary hypertension. The lack of anesthetic-related deaths in children who did not have major comorbidities reinforces the safety of pediatric anesthesia in healthy children.

Footnotes Funding: Hospital funded.

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Accepted January 21, 2011. Copyright ? 2011 International Anesthesia Research Society ? Previous | Next Article ?Table of Contents This Article Published online before print May 4, 2011, doi: 10.1213/?ANE.0b013e318213be52 A & A June 2011 vol. 112 no. 6 1440-1447 ? Abstract Full Text Full Text (PDF) CME Classifications Pediatric 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 van der Griend, B. F. Articles by Davidson, A. J. PubMed PubMed citation Articles by van der Griend, B. F. Articles by Davidson, A. J. Related Content Outcomes Patient Safety Pediatrics Load related web page information 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 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? The Role of Interleukin-1 in Wound Biology. Part I: Murine In Silico and In Vitro Experimental Analysis ? 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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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 . 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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 ? 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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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