Cellular mechanisms of ion and acid-base regulation in teleost gill ionocytes.

The mechanism(s) of sodium, chloride and pH regulation in teleost fishes has been the subject of intense interest for researchers over the past 100 years. The primary organ responsible for ionoregulatory homeostasis is the gill, and more specifically, gill ionocytes. Building on the theoretical and experimental research of the past, recent advances in molecular and cellular techniques in the past two decades have allowed for substantial advances in our understanding of mechanisms involved. With an increased diversity of teleost species and environmental conditions being investigated, it has become apparent that there are multiple strategies and mechanisms employed to achieve ion and acid-base homeostasis. This review will cover the historical developments in our understanding of the teleost fish gill, highlight some of the recent advances and conflicting information in our understanding of ionocyte function, and serve to identify areas that require further investigation to improve our understanding of complex cellular and molecular machineries involved in iono- and acid-base regulation.

Postoperative Nausea and Vomiting in Pediatric Patients.

Postoperative nausea and vomiting (PONV), postoperative vomiting (POV), post-discharge nausea and vomiting (PDNV), and opioid-induced nausea and vomiting (OINV) continue to be causes of pediatric morbidity, delay in discharge, and unplanned hospital admission. Research on the pathophysiology, risk assessment, and therapy for PDNV, OINV and pain therapy options in children has received increased attention. Multimodal pain management with the use of perioperative regional and opioid-sparing analgesia has helped decrease nausea and vomiting. Two common emetogenic surgical procedures in children are adenotonsillectomy and strabismus repair. Although PONV risk factors differ between adults and children, the approach to decrease baseline risk is similar. As PONV and POV are frequent in children, antiemetic prophylaxis should be considered for those at risk. A multimodal approach for antiemetic and pain therapy involves preoperative risk evaluation and stratification, antiemetic prophylaxis, and pain management with opioid-sparing medications and regional anesthesia. Useful antiemetics include dexamethasone and serotonin 5-hydroxytryptamine-3 (5-HT3) receptor antagonists such as ondansetron. Multimodal combination prophylactic therapy using two or three antiemetics from different drug classes and propofol total intravenous anesthesia should be considered for children at high PONV risk. "Enhanced recovery after surgery" protocols include a multimodal approach with preoperative preparation, adequate intravenous fluid hydration, opioid-sparing analgesia, and prophylactic antiemetics. PONV guidelines and management algorithms help provide effective postoperative care for pediatric patients.

New insights into the pathophysiology and risk factors for PONV.

Postoperative nausea and vomiting (PONV) affects patient outcomes and satisfaction. New research has centered on evaluation of post-discharge and opioid-related nausea and vomiting. Mechanical and drug effects stimulate the release of central nervous system neurotransmitters acting at receptors in the vomiting center, area postrema, and nucleus of the solitary tract. Brain surgery has allowed insight into specific central emetogenic areas. Stimuli from peripheral organs act through afferent vagus neurons and a parasympathetic response causing nausea and vomiting. Opioids stimulate mu receptors in the chemoreceptor trigger zone and cholinergic receptors in the vestibular system. Opioids also affect gastrointestinal (GI) tract mechanics by decreasing gastric emptying, intestinal motility, GI peristalsis, and secretions. Regional blocks and non-opioid multimodal analgesia help to decrease nausea and vomiting. Patient, surgery, and anesthesia factors contribute to risk and degree of PONV experienced. Pharmacogenetics plays a role in gene typing as antiemetic medication metabolism results in varying drug effectiveness. Risk scoring systems are available. Individualized multimodal plans can be designed as part of an enhanced recovery after surgery protocol.

Fourth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting.

This consensus statement presents a comprehensive and evidence-based set of guidelines for the care of postoperative nausea and vomiting (PONV) in both adult and pediatric populations. The guidelines are established by an international panel of experts under the auspices of the American Society of Enhanced Recovery and Society for Ambulatory Anesthesia based on a comprehensive search and review of literature up to September 2019. The guidelines provide recommendation on identifying high-risk patients, managing baseline PONV risks, choices for prophylaxis, and rescue treatment of PONV as well as recommendations for the institutional implementation of a PONV protocol. In addition, the current guidelines focus on the evidence for newer drugs (eg, second-generation 5-hydroxytryptamine 3 [5-HT3] receptor antagonists, neurokinin 1 (NK1) receptor antagonists, and dopamine antagonists), discussion regarding the use of general multimodal PONV prophylaxis, and PONV management as part of enhanced recovery pathways. This set of guidelines have been endorsed by 23 professional societies and organizations from different disciplines (Appendix 1).Guidelines currently available include the 3 iterations of the consensus guideline we previously published, which was last updated 6 years ago; a guideline published by American Society of Health System Pharmacists in 1999; a brief discussion on PONV management as part of a comprehensive postoperative care guidelines; focused guidelines published by the Society of Obstetricians and Gynecologists of Canada, the Association of Paediatric Anaesthetists of Great Britain & Ireland and the Association of Perianesthesia Nursing; and several guidelines published in other languages.The current guideline was developed to provide perioperative practitioners with a comprehensive and up-to-date, evidence-based guidance on the risk stratification, prevention, and treatment of PONV in both adults and children. The guideline also provides guidance on the management of PONV within enhanced recovery pathways.The previous consensus guideline was published 6 years ago with a literature search updated to October 2011. Several guidelines, which have been published since, are either limited to a specific populations or do not address all aspects of PONV management. The current guideline was developed based on a systematic review of the literature published up through September 2019. This includes recent studies of newer pharmacological agents such as the second-generation 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, a dopamine antagonist, neurokinin 1 (NK1) receptor antagonists as well as several novel combination therapies. In addition, it also contains an evidence-based discussion on the management of PONV in enhanced recovery pathways. We have also discussed the implementation of a general multimodal PONV prophylaxis in all at-risk surgical patients based on the consensus of the expert panel.

The introduction of gas warfare and its medical response in world war one.

The introduction of gas warfare in World War One was impactful, as it both expanded the breadth of warfare and fueled the invention of techniques required to treat these new injuries. Gas injuries were responsible for 91,000 of 1.3 million deaths in World War One. Gassed soldiers had wounds which the world had never seen. They presented in large scale to medical tents and base hospitals across Europe. As gas casualties poured in, doctors and nurses had to treat these conditions in the best way they knew. Gas warfare changed how war was performed and how casualties of this attack were treated. The techniques learned from treating the multitudes of men with gas burns led to advances in the field of burn care, which have helped to improve mortality and reduce morbidity in hospitals across the world.

Sedation and Analgesia for Adult Outpatient Burn Dressing Change: A Survey of American Burn Association Centers.

The management of pain and sedation during burn dressing change is challenging. Previous reviews and studies have identified wide variability in such practices in hospitalized burn patients. This survey-based study aimed to determine the most commonly utilized sedation and analgesia practices in adult burn patients treated in the outpatient setting. The goal was to identify opportunities for improvement and to assist burn centers in optimizing sedation procedures. A 23-question survey was sent to members of the American Burn Association. Nonpharmacological interventions including music, television, games, and virtual reality were used by 68% of survey respondents. Eighty-one percent reported premedicating with oral opioids, 32% with intravenous opioids, and 45% with anxiolytics. Fifty-nine percentage of respondents indicated that the initial medication regimen for outpatient dressing changes consisted of the patient's existing oral pain medications. Forty-three percent indicated that there were no additional options if this regimen provided inadequate analgesia. Fifty-six percentage of respondents felt that pain during dressing change was adequately controlled 75% to 100% of the time, and 32% felt it was adequately controlled 50% to 75% of the time. Nitrous oxide was used by 8%. Anesthesia providers and an acute pain service are available in a minority of cases (13.7% and 28%, respectively) and are rarely consulted. Procedural burn pain remains significantly undertreated in the outpatient setting and the approach to treatment is variable among burn centers in the United States. Such variation likely represents an opportunity for identifying and implementing optimal practices and developing guidelines for burn pain management in the outpatient setting.

Horst Otto Stoeckel: Clinician, Administrator, Researcher.

Horst Otto Stoeckel was born September 26, 1930, in Lodz, Poland, which was part of the newly founded Second Republic of Poland until it was occupied by Nazi Germany in 1939. After World War II, his family immigrated to Meiningen, Germany, where he obtained his primary and secondary education. He attended Humboldt University and the University Hospital Charité of Berlin for his medical degree. Profs Theodor Brugsch, Karl Lohmann, and Friedrich Dost were important individuals who helped develop his interest in quantitative clinical pharmacology and pharmacokinetics. Prior to anesthesiology, Stoeckel trained in surgery, internal medicine, and obstetrics and gynecology in addition to clinical anesthesiology at a community hospital in East Germany. He completed 2 years of obligatory training to become an anesthesia specialist at the Teaching Hospital Hufeland and the Research Institute for Lung Diseases at Berlin-Buch. He also received training in anesthesia at the Humboldt University of Berlin. After escaping East Berlin through the Brandenburg Gate in August 1961, he obtained a position at the University of Heidelberg and obtained his West German board certification in anesthesiology in 1962. In the following 12-year period, Stoeckel was married, was promoted, passed his "habilitation" or lectureship period, started a family, and was granted the title of "Professor." His administrative career began in February 1974 when he was selected as the first Chair of Anesthesiology at the University of Bonn, a position he held for 22 years. He also served as Dean of the medical school from 1980 to 1981. As Chair, he developed three areas: patient care, teaching, and research. He developed a long-term research program in the field of "Quantitative Clinical Pharmacology in Anesthesia and the Quantitative Modeling and Control in Anesthesia," which required an interdisciplinary team of specialists in biochemistry, physics, and modern analytical methods. Over 20 years, the group's research program led to the discovery of basic algorithms providing the foundation of the automatic regulation of dosing control by the closed-loop feedback system, which is a concept important to the target-controlled infusion of intravenous and inhalation anesthetics. Following his career as a clinician, administrator, and researcher, he pursued a second career as a collector and museum founder.

Horst Otto Stoeckel: Collector and Museum Founder.

As a medical student and during his preacademic time prior to 1958, Horst Stoeckel was interested in the history of medicine and especially history related to anesthesia. After his retirement from Chair of Anesthesiology at the University of Bonn in 1994, Stoeckel received a gift from Professor Richard Kitz of Harvard University (Boston, MA) that encouraged him to develop his collection of 150 artifacts and 350 books and periodicals into a scientific museum and library. The late librarian, Patrick P. Sim, MLS, of the Wood Library-Museum of Anesthesiology in the United States also encouraged and supported Stoeckel with literature concerning anesthesia history. The Horst Stoeckel Museum of Anaesthesiology (Horst-Stoeckel-Museum fur die Geschichte der Anasthesiologie) was dedicated by the University of Bonn and opened to the public on October 9, 2000, and currently has more than 1000 items displayed in 45 themed display cases. A newly themed concept of Incremental Development of Eminent Anesthesia Landmarks to Operational Routine was developed for the display and explanation of the history of anesthesia related to pioneers, equipment, books, and manuscripts. A display concept combining Person, Publication, and Apparatus is used throughout the museum. A well-stocked library currently holds more than 13,000 books and periodicals. The museum's 10-year anniversary was celebrated with a symposium entitled "German Pioneers in Anaesthesia of the first 100 years," held at the University of Bonn on October 8, 2010. The museum's Web site in German, English, and French is www.anaesthesia-museum.uni-bonn.de.

Sedation and Analgesia During Pediatric Burn Dressing Change: A Survey of American Burn Association Centers.

Sedation practices for pediatric burn patients during dressing changes vary between institutions and providers. To better understand the current trends in pediatric sedation practice, a survey was conducted among the members of the American Burn Association (ABA). Questions asked about nonoperating room sedation and analgesia practices for burn patients (ages 0-17) having dressing changes in the intensive care unit, inpatient unit, and outpatient clinics. ABA members providing sedation for pediatric patients undergoing burn dressing changes are diverse. Physician respondents included surgeons, critical care intensivists, and anesthesiologists. Others included physician assistants, nurse anesthetists, nurse practitioners, and sedation credentialed nurses. Opioids for pain control were prescribed by 100% of respondents, but use of adjuvant nonopioid analgesics was utilized <50% of the time. Benzodiazepines and ketamine were prescribed more than twice as often as other sedatives. Many noted that up to 50% of children did not have adequately controlled anxiety and pain with initial sedation plans, and escalation of care was needed to complete dressing changes. Self-reported adverse events were infrequent. In outpatient settings, benzodiazepines, ketamine, oral opioids, and topical lidocaine were used frequently, as were nonpharmacologic methods of distraction and comfort. Sedation in pediatric burn patients is challenging. Responses highlighted areas for improvement regarding pain control during dressing changes and increasing use of multimodal analgesia. Commonly used medications including opioids, benzodiazepine, and ketamine are well established in the treatment of burn patients, as are nonpharmacologic methods. A collaborative effort among institutions is needed to formulate practice guidelines for sedation during burn dressing changes.

Amisulpride Prevents Postoperative Nausea and Vomiting in Patients at High Risk: A Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Postoperative nausea and vomiting causes distress for patients and can prolong care requirements. Consensus guidelines recommend use of multiple antiemetics from different mechanistic classes as prophylaxis in patients at high risk of postoperative nausea and vomiting. The prophylactic efficacy of the dopamine D2/D3 antagonist amisulpride in combination with other antiemetics was investigated. METHODS: This double-blind, randomized, placebo-controlled, international, multicenter trial was conducted in 1,147 adult surgical patients having three or four postoperative nausea and vomiting risk factors. Patients were randomized to receive either intravenous amisulpride (5 mg) or matching placebo at induction of general anesthesia, in addition to one standard, nondopaminergic antiemetic, most commonly ondansetron or dexamethasone. Vomiting/retching, nausea, and use of rescue medication were recorded for 24 h after wound closure. The primary endpoint was complete response, defined as no emesis or rescue medication use in the 24-h postoperative period. RESULTS: Complete response occurred in 330 of 572 (57.7%) of the amisulpride group and 268 of 575 (46.6%) of the control group (difference 11.1 percentage points; 95% CI, 5.3 to 16.8; P < 0.001). The incidences of emesis (13.8% vs. 20.0%, P = 0.003), any nausea (50.0% vs. 58.3%, P = 0.002), significant nausea (37.1% vs. 47.7%, P < 0.001), and rescue medication use (40.9% vs. 49.4%, P = 0.002) were significantly lower in the amisulpride group. Adverse events and laboratory and electrocardiogram abnormalities occurred no more frequently with amisulpride than with placebo. CONCLUSIONS: Intravenous amisulpride was safe and effective as prophylaxis of postoperative nausea and vomiting when given in combination with an antiemetic from another class to adult patients at high risk for suffering postoperative nausea and vomiting undergoing elective surgery under inhalational general anesthesia. VISUAL ABSTRACT: An online visual overview is available for this article at http://links.lww.com/ALN/B727.

Procaine and Local Anesthetic Toxicity: A Collaboration Between the Clinical and Basic Sciences.

In 1924, the Therapeutic Research Committee of the American Medical Association appointed a special committee to investigate deaths following the administration of local anesthetics. The Committee for the Study of Toxic Effects of Local Anesthetics found procaine, although a safer clinical alternative to cocaine, was capable of causing death when large doses were injected into tissues and advised that it should be used with caution. This article describes a collaboration beginning in 1928 between Dr John Lundy of the Mayo Clinic and Dr Robert Isenberger of the University of Kansas, which arose from a controversy surrounding systemic adverse reactions to procaine. Isenberger then traveled to the Mayo Clinic to conduct research on various procaine local and spinal anesthesia doses and sodium amytal's protective effect against procaine-induced toxicity. Lundy and Isenberger's work would add to the ongoing discovery of systemic reactions to local anesthetics.

Intravenous Amisulpride for the Prevention of Postoperative Nausea and Vomiting: Two Concurrent, Randomized, Double-blind, Placebo-controlled Trials.

BACKGROUND: Two essentially identical, randomized, double-blind, placebo-controlled, parallel-group phase III studies evaluated the efficacy of intravenous amisulpride, a dopamine D2/D3 antagonist, in the prevention of postoperative nausea and vomiting in adult surgical patients. METHODS: Adult inpatients undergoing elective surgery during general anesthesia and having at least two of the four Apfel risk factors for postoperative nausea and vomiting were enrolled at 9 U.S. and 10 European sites. A single 5-mg dose of amisulpride or matching placebo was given at induction of anesthesia. The primary endpoint was complete response, defined as no vomiting/retching and no use of antiemetic rescue medication in the 24-h postoperative period. Nausea incidence was a secondary endpoint. RESULTS: Across the two studies, 689 patients were randomized and dosed with study medication, of whom 626 were evaluable per protocol. In the U.S. study, 46.9% (95% CI, 39.0 to 54.9) of patients achieved complete response in the amisulpride group compared to 33.8% (95% CI, 26.2 to 42.0) in the placebo group (P = 0.026). In the European study, complete response rates were 57.4% (95% CI, 49.2 to 65.3) for amisulpride and 46.6% (95% CI, 38.8 to 54.6) for placebo (P = 0.070). Nausea occurred less often in patients who received amisulpride than those who received placebo. There was no clinically significant difference in the safety profile of amisulpride and placebo; in particular, there were no differences in terms of QT prolongation, extrapyramidal side effects, or sedation. CONCLUSIONS: One of the two trials demonstrated superiority, while pooling both in a post hoc change to the plan of analysis supported the hypothesis that amisulpride was safe and superior to placebo in reducing the incidence of postoperative nausea and vomiting in a population of adult inpatients at moderate to high risk of postoperative nausea and vomiting.

Sedation and Analgesia for Dressing Change: A Survey of American Burn Association Burn Centers.

Pain and sedation management for patients undergoing burn dressing change can be challenging. Variations appear to exist in the selection of medications before and during burn dressing change. To determine if institutional variations exist in pain and sedation management for burn dressing change, an online survey was sent to ABA Burn Center nurses and physicians. Three hundred seventy-eight anonymous responses were received from nurses (72%), nurse practitioners (10%), and physicians (18%). Burn centers had adult (22%), pediatric (12%), or pediatric and adult (66%) patients. Eighty percentage of centers had >200 patients/year. Sixty-eight percentage always used a premedication. Oxycodone and morphine or fentanyl was the most frequently used per oral (PO) and intravenous (IV) opioid premedication, respectively. The most common IV premedication anxiolytic were benzodiazepines. Sixty-eight percentage always used a long-acting opioid. Anesthetic regimen was decided case-by-case (47%) or specific protocol (24%). Protocol was followed always (18%) or mostly (55%). Patients' procedural pain could be better controlled 20% of the time. Pain regimen was altered most of the time (25%). Providers differed rarely (39%) and sometimes (44%) regarding preferred regimen. Ketamine was the most common deep sedative. A dedicated anesthesiologist was rarely (33%) consulted, determined case-by-case (33%) or prior failure/excess pain (19%). Acute pain service was never (51%) or rarely (35%) consulted. Pain and sedation management for burn dressing change is difficult and variations in approach exist among burn centers. Such management needs individualized care. Providers must be responsive to pain alterations. Consultation with anesthesia providers may be needed in specific cases. Further studies need to be completed to demonstrate the most effective means of controlling burn pain and evaluating patient outcomes.

Comparative Pharmacology and Guide to the Use of the Serotonin 5-HT3 Receptor Antagonists for Postoperative Nausea and Vomiting.

Since the introduction of the serotonin 5-hydroxy tryptamine 3 (5-HT3) receptor antagonists in the early 1990s, the incidence of postoperative nausea and vomiting (PONV) and post-discharge nausea and vomiting (PDNV) has decreased, yet continues to be a problem for the surgical patient. The clinical application of the 5-HT3 receptor antagonists has helped define the approach and role of these antiemetics in the prevention and treatment of PONV and PDNV. Pharmacological and clinical differences exist among these medications resulting in corresponding differences in effectiveness, safety, optimal dosage, time of administration, and use as combination and rescue antiemetic therapy. The clinical application of the 5-HT3 receptor antagonist antiemetics has improved the prevention and treatment of PONV and PDNV. The most recent consensus guidelines for PONV published in 2014 outline the use of these antiemetics. The 5-HT3 receptor antagonists play an important role to help prevent PONV and PDNV in perioperative care pathways such as Enhanced Recovery After Surgery (ERAS). Comparisons and guidelines for use of the 5-HT3 receptor antagonists in relation to the risk for PONV and PDNV are reviewed.

Cortical Effects on Ipsilateral Hindlimb Muscles Revealed with Stimulus-Triggered Averaging of EMG Activity.

While a large body of evidence supports the view that ipsilateral motor cortex may make an important contribution to normal movements and to recovery of function following cortical injury (Chollet et al. 1991; Fisher 1992; Caramia et al. 2000; Feydy et al. 2002), relatively little is known about the properties of output from motor cortex to ipsilateral muscles. Our aim in this study was to characterize the organization of output effects on hindlimb muscles from ipsilateral motor cortex using stimulus-triggered averaging of EMG activity. Stimulus-triggered averages of EMG activity were computed from microstimuli applied at 60-120 µA to sites in both contralateral and ipsilateral M1 of macaque monkeys during the performance of a hindlimb push-pull task. Although the poststimulus effects (PStEs) from ipsilateral M1 were fewer in number and substantially weaker, clear and consistent effects were obtained at an intensity of 120 µA. The mean onset latency of ipsilateral poststimulus facilitation was longer than contralateral effects by an average of 0.7 ms. However, the shortest latency effects in ipsilateral muscles were as short as the shortest latency effects in the corresponding contralateral muscles suggesting a minimal synaptic linkage that is equally direct in both cases.

Safety and efficacy of commonly used antiemetics.

INTRODUCTION: Clinicians use antiemetic drugs in a multitude of scenarios. Despite the differences in subspecialty and etiology of the nausea, practitioners of all subspecialties use the same drugs in similar ways to provide relief for their patients. AREAS COVERED: Multiple classes of antiemetics are used frequently but no single treatment course works for all types of patients. The complex etiology of nausea often requires a multimodal approach that targets the same symptom through different sites of action. Antiemetics have unique side effects and safety profiles which are covered in this review. Antihistamines, phenothiazines, corticosteroids, benzamindes, anticholinergic, neurokinin-1 antagonists, 5-HT3 receptor antagonist and cannabinoids are discussed. These drugs were evaluated based on an in-depth literature review including a review of the original research that led to many of the drugs initial FDA approval, via internet and PubMed searches. EXPERT OPINION: The key to providing relief for patients suffering from nausea and vomiting is to consider multiple drugs to approach the nausea in a systematic way. Anesthesiologists identify patients who are at high risk of nausea and vomiting based on physical characteristics and surgical procedures. Oncologists treat nausea based on the prescribed chemotherapeutics regimen and known risk of emesis while palliative care physicians and others balance the etiology of the nausea while optimizing patients other co morbid conditions.

Walter sutton: physician, scientist, inventor.

Walter S. Sutton (1877-1916) was a physician, scientist, and inventor. Most of the work on Sutton has focused on his recognition that chromosomes carry genetic material and are the basis for Mendelian inheritance. Perhaps less well known is his work on rectal administration of ether. After Sutton's work on genetics, he completed his medical degree in 1907 and began a 2-year surgical fellowship at Roosevelt Hospital, New York City, NY, where he was introduced to the technique of rectal administration of ether. Sutton modified the work of others and documented 100 cases that were reported in his 1910 landmark paper "Anaesthesia by Colonic Absorption of Ether". Sutton had several deaths in his study, but he did not blame the rectal method. He felt that his use of rectal anesthesia was safe when administered appropriately and believed that it offered a distinct advantage over traditional pulmonary ether administration. His indications for its use included (1) head and neck surgery; (2) operations when ether absorption must be minimized due to heart, lung, or kidney problems; and (3) preoperative pulmonary complications. His contraindications included (1) cases involving alimentary tract or weakened colon; (2) laparotomies, except when the peritoneal cavity was not opened; (3) incompetent sphincter or anal fistula; (4) orthopnea; and (5) emergency cases. Sutton wrote the chapter on "Rectal Anesthesia" in one of the first comprehensive textbooks in anesthesia, James Tayloe Gwathmey's Anesthesia. Walter Sutton died of a ruptured appendix in 1916 at age 39.