The arousal effect of An-Gong-Niu-Huang-Wan on alcoholic-induced coma rats: A research based on EEG.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute alcohol intoxication is one of the leading causes of coma. A well-regarded Chinese herbal formula, known as An-Gong-Niu-Huang-Wan (AGNHW), has garnered recognition for its efficacy in treating various brain disorders associated with impaired consciousness, including acute alcohol-induced coma. Despite its clinical effectiveness, the scientific community lacks comprehensive research on the mechanistic aspects of AGNHW's impact on the electroencephalogram (EEG) patterns observed during alcohol-induced coma. Gaining a deeper understanding of AGNHW's mechanism of action in relation to EEG characteristics would hold immense importance, serving as a solid foundation for further advancing its clinical therapeutic application. AIM OF THE STUDY: The study sought to investigate the impact of AGNHW on EEG activity and sleep EEG patterns in rats with alcoholic-induced coma. MATERIALS AND METHODS: A rat model of alcohol-induced coma was used to examine the effects of AGNHW on EEG patterns. Male Sprague-Dawley rats were intraperitoneally injected with 32% ethanol to induce a coma, followed by treatment with AGNHW. Wireless electrodes were implanted in the cortex of the rats to obtain EEG signals. Our analysis focused on evaluating alterations in the Rat Coma Scale (RCS), as well as assessing changes in the frequency and distribution of EEG patterns, sleep rhythms, and body temperature subsequent to AGNHW treatment. RESULTS: The study found a significant increase in the δ-band power ratio, as well as a decrease in RCS scores and ß-band power ratio after modeling. AGNHW treatment significantly reduced the δ-band power ratio and increased the ß-band power ratio compared to naloxone, suggesting its superior arousal effects. The results also revealed a decrease in the time proportion of WAKE and REM EEG patterns after modeling, accompanied by a significant increase in the time proportion of NREM EEG patterns. Both naloxone and AGNHW effectively counteracted the disordered sleep EEG patterns. Additionally, AGNHW was more effective than naloxone in improving hypothermia caused by acute alcohol poisoning in rats. CONCLUSION: Our study provides evidence for the arousal effects of AGNHW in alcohol-induced coma rats. It also suggests a potential role for AGNHW in regulating post-comatose sleep rhythm disorders.

Effect of prehospital high-dose glucocorticoid on hemodynamics in patients resuscitated from out-of-hospital cardiac arrest: a sub-study of the STEROHCA trial.

BACKGROUND: Following resuscitated out-of-hospital cardiac arrest (OHCA), inflammatory markers are significantly elevated and associated with hemodynamic instability and organ dysfunction. Vasopressor support is recommended to maintain a mean arterial pressure (MAP) above 65 mmHg. Glucocorticoids have anti-inflammatory effects and may lower the need for vasopressors. This study aimed to assess the hemodynamic effects of prehospital high-dose glucocorticoid treatment in resuscitated comatose OHCA patients. METHODS: The STEROHCA trial was a randomized, placebo-controlled, phase 2 trial comparing one prehospital injection of methylprednisolone 250 mg with placebo immediately after resuscitated OHCA. In this sub-study, we included patients who remained comatose at admission and survived until intensive care unit (ICU) admission. The primary outcome was cumulated norepinephrine use from ICU admission until 48 h reported as mcg/kg/min. Secondary outcomes included hemodynamic status characterized by MAP, heart rate, vasoactive-inotropic score (VIS), and the VIS/MAP-ratio as well as cardiac function assessed by pulmonary artery catheter measurements. Linear mixed-model analyses were performed to evaluate mean differences between treatment groups at all follow-up times. RESULTS: A total of 114 comatose OHCA patients were included (glucocorticoid: n = 56, placebo: n = 58) in the sub-study. There were no differences in outcomes at ICU admission. From the time of ICU admission up to 48 h post-admission, patients in the glucocorticoid group cumulated a lower norepinephrine use (mean difference - 0.04 mcg/kg/min, 95% CI - 0.07 to - 0.01, p = 0.02). Moreover, after 12-24 h post-admission, the glucocorticoid group demonstrated a higher MAP with mean differences ranging from 6 to 7 mmHg (95% CIs from 1 to 12), a lower VIS (mean differences from - 4.2 to - 3.8, 95% CIs from - 8.1 to 0.3), and a lower VIS/MAP ratio (mean differences from - 0.10 to - 0.07, 95% CIs from - 0.16 to - 0.01), while there were no major differences in heart rate (mean differences from - 4 to - 3, 95% CIs from - 11 to 3). These treatment differences between groups were also present 30-48 h post-admission but to a smaller extent and with increased statistical uncertainty. No differences were found in pulmonary artery catheter measurements between groups. CONCLUSIONS: Prehospital treatment with high-dose glucocorticoid was associated with reduced norepinephrine use in resuscitated OHCA patients. TRIAL REGISTRATION: EudraCT number: 2020-000855-11; submitted March 30, 2020. URL: https://www. CLINICALTRIALS: gov ; Unique Identifier: NCT04624776.

Clinical Results of Accelerated Iontophoresis-Assisted Epithelium-on Corneal Cross-linking for Progressive Keratoconus in Children.

PURPOSE: To evaluate the clinical characteristics of pediatric patients with progression of keratoconus after accelerated iontophoresis-assisted epithelium-on corneal cross-linking (I-ON CXL) and to assess the efficacy and safety of re-treatment using accelerated epithelium-off CXL (epi-OFF CXL). METHODS: Sixteen eyes of 16 patients (mean age: 14.6 ± 2.5 years) with keratoconus underwent I-ON CXL. The main outcome measures were uncorrected distance visual acuity, corrected distance visual acuity, maximum keratometry index (Kmax), minimum corneal thickness, elevation front and elevation back measured at the thinnest point, total higher order aberrations root main square (HOA RMS), coma RMS, and spherical aberration. An increment of Kmax greater than 1.00 diopter (D) and a decrease of greater than 20 µm in pachymetry were considered to determine the progression of keratoconus. Patients with progression of keratoconus after I-ON CXL were re-treated using an epi-OFF CXL protocol. RESULTS: Two years after I-ON CXL, 12 patients showed progression of keratoconus, whereas 4 patients were stable. There was significant worsening of Kmax (P = .04) and steepest keratometric reading (P = .01). Furthermore, a significant correlation was documented between progression of keratoconus and age (P = .02). These patients were re-treated using an epi-OFF protocol and after 2 years all patients were stable, and a statistically significant reduction of the mean Kmax (P = .007), HOA RMS (P = .05), and coma RMS (P = 05) was observed. CONCLUSIONS: I-ON CXL was ineffective in the treatment of pediatric keratoconus in younger children, whereas it had an efficacy of 2 years in older children. Re-treatment using epi-OFF CXL proved effective to halt progression of keratoconus after I-ON CXL failure. [J Pediatr Ophthalmol Strabismus. 2024;61(1):44-50.].

Clinical characteristics of acute lacosamide poisoning: Pavia Poison Control Centre experience.

AIMS: Lacosamide is a third-generation antiepileptic drug used as adjunctive therapy for partial seizures. Since its approval in 2008 very few cases of lacosamide overdose have been described in literature. The aim of our study was to evaluate clinical characteristics of acute lacosamide poisoning. METHODS: A retrospective observational study was performed including all cases of acute lacosamide poisoning referred to Pavia Poison Control Centre from January 2012 to December 2021. For each patient age, sex, ingested dose, coingestants, clinical manifestations, treatment and outcome were collected. RESULTS: A total of 31 subjects (median age 39 years, [interquartile range: 26.5-46.5]; females 22/31) were included. The median lacosamide ingested dose was 1500 mg [650-2800]. In 35.5% of cases lacosamide was the single ingested substance, while in 64.5% coingestants were also present. Coingestants varied from a minimum of 1 to a maximum of 3, with the more common being benzodiazepines and valproic acid. Clinical manifestations were present in 87% patients the most common were: vomiting (29%); seizures (29%), coma (25.8%), drowsiness (25.8%), confusion (12.9%), agitation (12.9%), tachycardia (12.9%), tremors (9.7%), bradycardia (9.7%), headache (6.5%) and hypertension (3.2%). The median lacosamide ingested dose was significantly higher in patients that experienced coma compared to patient who did not (2800 vs. 800 mg; P = .0082). Orotracheal intubation was necessary in 32.3% of patients. All patients fully recovered. CONCLUSION: Lacosamide acute overdose may lead to a severe clinical picture. Dentral nervous system symptoms predominated, particularly seizures and coma occurred in a high percentage of cases.

Piperacillin-Tazobactam Versus Anti-Pseudomonal Cephalosporins and Renal and Neurologic Outcomes in Critically Ill Adults: A Secondary Analysis of the SMART Trial.

Background: Prior studies suggest associations between receipt of piperacillin-tazobactam and development of acute kidney injury and receipt of anti-pseudomonal cephalosporins and neurotoxicity. We compared clinically-relevant renal and neurologic outcomes in critically ill patients who received piperacillin-tazobactam versus anti-pseudomonal cephalosporins. Methods: We conducted a secondary analysis of data from the Isotonic Solutions and Major Adverse Renal Events Trial examining patients who received piperacillin-tazobactam or an anti-pseudomonal cephalosporin within 24 h of intensive care unit admission. We performed multivariable analysis using a proportional odds model to examine the association between the first antibiotic received and the outcomes of Major Adverse Kidney Events within 30 days (MAKE30) and days alive and free of delirium and coma to day 28. Results: 3199 were included in the study; 2375 (74%) receiving piperacillin-tazobactam and 824 (26%) receiving anti-pseudomonal cephalosporin. After adjustment for prespecified confounders, initial receipt of piperacillin-tazobactam, compared to anti-pseudomonal cephalosporins, was not associated with higher incidence of MAKE30 (adjusted odds ratio, 1.03; 95% CI, 0.83-1.27; P = .80) but was associated with a greater number of days alive and free of delirium and coma (adjusted odds ratio, 1.18; 95% CI, 1.00-1.38; P = .04). In a sensitivity analysis adjusting for baseline receipt of medications which may impact neuro function, this finding was not significant. Conclusion: Among critically ill adults, receipt of piperacillin-tazobactam was not associated with an increased incidence of death, renal replacement therapy, or persistent renal dysfunction or a greater number of days alive and free of delirium and coma. Randomized trials are needed to inform the choice of antibiotics for empiric treatment infection in critically ill adults.

Liquid levothyroxine in the treatment of myxoedema coma.

Not required for Clinical Vignette.

Role of Hemodialysis in Acute Severe Alcohol Intoxication: A Meta-Analysis.

BACKGROUND: Hemodialysis therapy has been used in the treatment of acute alcohol intoxication for many years, especially acute severe alcohol intoxication. OBJECTIVES: This study aimed to evaluate whether the combination of conventional treatment and naloxone with hemodialysis has advantages over conventional treatment and naloxone alone in patients with acute severe alcohol intoxication. METHODS: After searching 12 databases and 2 clinical trial centers. According to the established inclusion and exclusion criteria, the qualified literatures were screened. The outcome indicators were length of hospital stay, coma time, time of symptom disappearance, the overall complication rate, the incidence of pancreatitis, the incidence of aspiration pneumonia, the incidence of hepatic and renal dysfunction. Analysis was performed using Revman 5.3. RESULTS: This meta-analysis included 13 studies, including 932 subjects. In the treatment of acute severe alcohol intoxication, the use of hemodialysis on the basis of conventional treatment and naloxone could reduce the length of hospital stay (WMD = -15.16, 95% CI: -17.45 to -12.86, p < 0.001) in hours and (WMD = -4.89, 95% CI: -5.53 to -4.25, p < 0.001) in days; coma time (WMD = -5.43, 95% CI: -6.43 to -4.43, p < 0.001); time of symptom disappearance (WMD = -3.92, 95% CI: -5.37 to -2.47, p < 0.001); the overall complication rate (RR = 0.39, 95% CI: 0.28-0.55, p < 0.001); the incidence of pancreatitis (RR = 0.14, 95% CI: 0.05-0.43, p = 0.0006); the incidence of aspiration pneumonia (RR = 0.15, 95% CI: 0.04-0.66, p = 0.01), and the incidence of hepatic and renal dysfunction (RR = 0.21, 95% CI: 0.06-0.72, p = 0.01). CONCLUSIONS: It can be concluded that compared with the use of conventional treatment and naloxone alone, the use of hemodialysis on the basis of conventional treatment and naloxone for acute severe alcohol intoxication can reduce the length of hospital stay, coma time, time of symptom disappearance, and the incidence of some complications rate. Large scale, multicenter, and well-designed RCTs are needed in the future to prove our conclusions.

Home management of pediatric sulfonylurea ingestions.

INTRODUCTION: Sulfonylureas are oral antidiabetic medications that act by stimulating insulin release from pancreatic beta cells. Unintentional pediatric ingestions may result in hypoglycemia. While guidelines often recommend up to a 24-hour hospital observation period for any ingestion, the Oregon Poison Center has historically managed select patients at home. This study aimed to describe outcomes of home-managed pediatric sulfonylurea exposures and characteristics of ingestions that are appropriate for home monitoring. METHODS: This is a retrospective chart review of pediatric (≤5 years) sulfonylurea ingestions in a single poison center over a 19-year period (2002-2020). We reviewed 491 individual cases for age, ingestion quantity, witnessed or unwitnessed ingestions, hypoglycemia (<60 mg/dL), disposition, and severe events (seizures or coma). We excluded cases in which missing pills were later found or another agent was identified. RESULTS: Of 474 patients meeting inclusion criteria, 135 (28%) were initially managed at home. Of these, 115 (85.3%) were ingestions of ≤1 tablet, where 68 (59%) were witnessed and 47 (41%) were unwitnessed. One hundred twenty five (92.6%) of these patients were successfully monitored at home, with 10 (7%) ultimately referred to a healthcare facility (HCF). Symptoms of hypoglycemia, measured glucose on home meter <60 mg/dL, fluctuations in monitored glucose, or parental concern were indications for HCF referral. Of those referred, 5 (4%) developed uncomplicated, asymptomatic hypoglycemia. Two of these received octreotide, at the discretion of the treating physician. No patients developed seizures or coma. DISCUSSION: We report 135 pediatric sulfonylurea ingestions managed with initial home monitoring, the majority of which were successfully monitored at home without any reported adverse events. Ten patients "failed home monitoring," as defined by referral to a healthcare facility. Of these, five developed hypoglycemia, though no patients developed symptoms or serious adverse events. CONCLUSION: Our findings support home observation for children ≤5 years with small ingestions of second-generation sulfonylureas.

Myxedema coma: Recognition and treatment.

ABSTRACT: Myxedema coma (MC) develops from a long-standing, unrecognized, or untreated hypothyroidism. This article discusses the pathophysiology, clinical manifestations, treatment, and nursing considerations for patients with MC.

Corneal higher-order aberration changes after accelerated cross-linking for keratoconus.

AIM: To evaluate changes in corneal higher-order aberrations (HOAs) following epithelium-off accelerated corneal cross-linking (A-CXL) and to explore the impact on visual acuity. METHODS: In this retrospective case series, 32 eyes of 24 patients with keratoconus (KC) underwent A-CXL. Treatment was delivered at 10 mW/cm2 for 9 min with a total dose of 5.4 J/cm2. The following anterior corneal HOAs: total corneal HOAs, trefoil, secondary trefoil, coma, secondary coma, secondary astigmatism and spherical aberrations were analysed using the Scheimpflug-Placido Sirius (CSO, Italy) corneal topographer at baseline and 12 months following treatment. Multivariate analysis was used to evaluate the independent effect of HOA subtypes on changes in uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA). RESULTS: At one year post CXL, UDVA and CDVA were significantly improved, -0.13 ± 0.19 LogMAR (P = 0.0005) and -0.08 ± .0.11 LogMAR (P = 0.0003), respectively. The mean preoperative trefoil, secondary trefoil, secondary coma and secondary astigmatism were 0.95 ± 0.46; µm, 0.20 ± 0.11; µm, 0.29 ± 0.19; µm and 0.42 ± 0.17 µm, respectively. At one year, the mean values decreased significantly to 0.77 ± 0.47 µm, 0.15 ± 0.11 µm, 0.25 ± 0.18 µm and 0.34 ± 0.18 µm, respectively (P < 0.05, for all). No independent relationship between any HOA changes and change in UDVA was observed. A reduction in secondary coma aberration was associated with a change in CDVA (95% CI 0.01-1.34, P = 0.048; ß = 0.67). CONCLUSION: A 9-min protocol of Accelerated corneal cross-linking is an effective treatment in improving corneal HOAs at 12 months follow up, in eyes with progressive keratoconus at one year follow-up. A change in secondary coma had a statistically significant and independent effect on CDVA.

Characteristics of circulatory failure after out-of-hospital cardiac arrest: a prospective cohort study.

BACKGROUND: Circulatory failure after out-of-hospital cardiac arrest (OHCA) as part of the postcardiac arrest syndrome (PCAS) is believed to be caused by an initial myocardial depression that later subsides into a superimposed vasodilatation. However, the relative contribution of myocardial dysfunction and systemic inflammation has not been established. Our objective was to describe the macrocirculatory and microcirculatory failure in PCAS in more detail. METHODS: We included 42 comatose patients after OHCA where circulatory variables were invasively monitored from admission until day 5. We measured the development in cardiac power output (CPO), stroke work (SW), aortic elastance, microcirculatory metabolism, inflammatory and cardiac biomarkers and need for vasoactive medications. We used survival analysis and Cox regression to assess time to norepinephrine discontinuation and negative fluid balance, stratified by inflammatory and cardiac biomarkers. RESULTS: CPO, SW and oxygen delivery increased during the first 48 hours. Although the estimated afterload fell, the blood pressure was kept above 65 mmHg with a diminishing need for norepinephrine, indicating a gradually re-established macrocirculatory homoeostasis. Time to norepinephrine discontinuation was longer for patients with higher pro-brain natriuretic peptide concentration (HR 0.45, 95% CI 0.21 to 0.96), while inflammatory biomarkers and other cardiac biomarkers did not predict the duration of vasoactive pressure support. Markers of microcirculatory distress, such as lactate and venous-to-arterial carbon dioxide difference, were normalised within 24 hours. CONCLUSION: The circulatory failure was initially characterised by reduced CPO and SW, however, microcirculatory and macrocirculatory homoeostasis was restored within 48 hours. We found that biomarkers indicating acute heart failure, and not inflammation, predicted longer circulatory support with norepinephrine. Taken together, this indicates an early and resolving, rather than a late and emerging vasodilatation. TRIAL REGISTRATION: NCT02648061.

The effect of Glibenclamide on somatosensory evoked potentials after cardiac arrest in rats.

BACKGROUND: Science continues to search for a neuroprotective drug therapy to improve outcomes after cardiac arrest (CA). The use of glibenclamide (GBC) has shown promise in preclinical studies, but its effects on neuroprognostication tools are not well understood. We aimed to investigate the effect of GBC on somatosensory evoked potential (SSEP) waveform recovery post CA and how this relates to the early prediction of functional outcome, with close attention to arousal and somatosensory recovery, in a rodent model of CA. METHODS: Sixteen male Wistar rats were subjected to 8-min asphyxia CA and assigned to GBC treatment (n = 8) or control (n = 8) groups. GBC was administered as a loading dose of 10 µg/kg intraperitoneally 10 min after the return of spontaneous circulation, followed by a maintenance dosage of 1.6 µg/kg every 8 h for 24 h. SSEPs were recorded from baseline until 150 min following CA. Coma recovery, arousal, and brainstem function, measured by subsets of the neurological deficit score (NDS), were compared between both groups. SSEP N10 amplitudes were compared between the two groups at 30, 60, 90, and 120 min post CA. RESULTS: Rats treated with GBC had higher sub-NDS scores post CA, with improved arousal and brainstem function recovery (P = 0.007). Both groups showed a gradual improvement of SSEP N10 amplitude over time, from 30 to 120 min post CA. Rats treated with GBC showed significantly better SSEP recovery at every time point (P < 0.001 for 30, 60, and 90 min; P = 0.003 for 120 min). In the GBC group, the N10 amplitude recovered to baseline by 120 min post CA. Quantified Cresyl violet staining revealed a significantly greater percentage of damage in the control group compared with the GBC treatment group (P = 0.004). CONCLUSIONS: Glibenclamide improves coma recovery, arousal, and brainstem function after CA with decreased number of ischemic neurons in a rat model. GBC improves SSEP recovery post CA, with N10 amplitude reaching the baseline value by 120 min, suggesting early electrophysiologic recovery with this treatment. This medication warrants further exploration as a potential drug therapy to improve functional outcomes in patients after CA.

Cognitive Impairment Following Clinical or Recreational Use of Gammahydroxybutyric Acid (GHB): A Systematic Review.

BACKGROUND: GHB (gamma-hydroxybutyric acid; sodium oxybate) is a general anaesthetic that is clinically used for the treatment of narcolepsy, cataplexy, alcohol withdrawal and alcohol relapse prevention. In addition, GHB is recreationally used. Most clinical and recreational users regard GHB as an innocent drug devoid of adverse effects, despite its high dependence potential and possible neurotoxic effects. At high doses, GHB may lead to a comatose state. This paper systematically reviews possible cognitive impairments due to clinical and recreational GHB use. METHODS: PubMed and PsychINFO were searched for literature data about the acute and residual cognitive deficits following GHB use. This review is conducted using the PRISMA protocol. RESULTS: A total of 43 reports covering human and animal data on GHB-induced cognitive impairments were eligible and reviewed. This systematic review found no indication for cognitive impairments after clinical GHB use. However, it supports the view that moderate GHB use may result in acute short-term cognitive impairments, whereas regular high-dose GHB use and/or multiple GHB-induced comas are probably neurotoxic resulting in long-term residual cognitive impairments. CONCLUSION: These results emphasize the need for awareness among clinicians and recreational users to minimize negative health consequences of recreational GHB use, particularly when high doses are used and GHB-induced comas occur.

Flumazenil therapy for a gabapentin-induced coma: a case report.

BACKGROUND: Spasticity and neuropathic pain are common in patients after spinal cord injury and negatively affect patients' quality of life. Gabapentin and baclofen are frequently used to treat these conditions. We present a flumazenil-reversed gabapentin-induced coma case, which, to our knowledge, is the second one described in scientific literature. CASE PRESENTATION: A 70-year-old Caucasian man was admitted to our neurorehabilitation ward following a fall with cervical trauma that resulted in immediate tetraplegia. During his stay, he suffered from lower limb pain, both neuropathic and due to severe spasticity. Gradual baclofen and gabapentin administration was prescribed, with reduction in both pain and spasticity. One morning, the patient was found unresponsive, with a Glasgow Coma Score of 3. Head computerized tomography, electrocardiogram, electroencephalogram, vital signs, blood tests, breathing, and blood oxygenation were normal. Renal and liver failure were ruled out. Intravenous 0.25 mg of flumazenil (Anexate) was administered, resulting in complete neurocognitive recovery with a Glasgow Coma Score of 15. DISCUSSION AND CONCLUSIONS: This case report highlights the importance of the individual response to certain pharmacological agents and suggests that further studies need to be conducted both on flumazenil and gabapentin pharmacodynamics to better understand their molecular-receptor activity, and on possible multiple flumazenil mechanisms of action, beyond its classical strict benzodiazepine antagonist action.

Central versus paracentral cone location and outcomes of accelerated cross-linking in keratoconus patients.

PURPOSE: To compare outcomes 1 year after accelerated cross-linking (CXL) between keratoconus eyes with central cones to those with paracentral cones. METHODS: In this post hoc analysis of data from a prospective multicentre study, consecutive progressive keratoconus eyes treated with accelerated CXL were included. Preoperative and 1 year post CXL manifest refraction, corneal cylinder, maximal keratometry (Kmax), central corneal thickness and coma were assessed. Central and paracentral cones were defined as cones within the central 3 mm and those between 3 and 5 mm, respectively. Eyes with apical scarring and peripheral cones (>5 mm) were excluded. The primary outcome measures were changes in best spectacle-corrected visual acuity (BSCVA) and Kmax. RESULTS: Overall, 314 eyes (n = 314) with a mean age of 27.5 ± 7.7 years were included. At baseline, the central cone group was younger (p < 0.001), had lower corneal astigmatism (p = 0.03) and coma (p = 0.02). At 1 year post CXL, after adjusting for baseline characteristics (age, BSCVA, corneal astigmatism, Kmax and coma), the central cone group showed a greater reduction in myopia (mean difference 1.27 ± 0.60D, p = 0.04) and more improvement in BSCVA (mean difference 0.08 ± 0.02 logMAR, p < 0.001) compared to the paracentral group. There was no significant difference in progression rates between the central and paracentral groups (ΔKmax > 2D, 6.7% vs. 6.5%, respectively, p = 0.83). CONCLUSIONS: This large-scale study of keratoconus eyes 1 year after accelerated CXL indicates that compared to those with paracentral cones, central cones have on average almost one additional line improvement in BCSVA and 1.27 D more reduction in myopia.

Successful treatment of severe, treatment resistant GHB withdrawal through thiopental-coma.

BACKGROUND: In patients with gamma-hydroxybutyrate (GHB) use disorder (GUD), withdrawal can have a fulminant course with rapid progression of severe, potentially life-threatening complications. Case: We present a 45-year old man with severe GHB withdrawal, resistant to conventional treatment with pharmaceutical GHB, high doses of benzodiazepines and baclofen. GHB withdrawal finally responded to thiopental-induced coma therapy, with burst suppression pattern on electroencephalography (EEG). The patient fully recovered, without withdrawal or residual neuropsychiatric symptoms. Discussion: To our knowledge, this is the first case report in which barbiturates were used to induce a coma to treat severe, treatment resistant GHB withdrawal. This case suggests barbiturate coma therapy might be considered in severe GHB withdrawal which does not respond to conventional treatment.

Clinical characteristics and time trends of hospitalized methadone exposures in the United States based on the Toxicology Investigators Consortium (ToxIC) case registry: 2010-2017.

BACKGROUND: Methadone is well known for its long duration of action and propensity for mortality after an overdose. The present research was aimed at evaluating the clinical manifestations and time trends of methadone exposure in patients in US hospitals. METHODS: We queried the American College of Medical Toxicology's Toxicology Investigators Consortium case registry for all cases of methadone exposure between January 1, 2010, and December 31, 2017. The collected information included demographic features, clinical presentations, therapeutic interventions, poisoning type (acute, chronic, or acute on chronic), and the reason(s) for exposure. Descriptive data and relative frequencies were used to investigate the participants' characteristics. Our data analysis was performed using SPSS version 19 and Prism software. The trends and clinical manifestations of methadone poisoning over the time period of the study were specifically investigated. RESULTS: Nine hundred and seventy-three patients who met our inclusion criteria, with a mean age of 41.9 ± 16.6 years (range: 11 months-78 years) were analyzed. Five hundred eighty-two (60.2%) were male. The highest rate of methadone poisoning was observed in 2013. There was an increasing rate of methadone exposures in 2010-2013, followed by a decline in 2014-2017. The most common clinical manifestations in methadone-poisoned patients were coma (48.6%) and respiratory depression (33.6%). The in-hospital mortality rate of methadone poisoning was 1.4%. CONCLUSION: ToxIC Registry data showed that inpatient methadone exposures enhanced from 2010 to 2013, after which a reduction occurred in the years 2014 to 2017.

Reversible bradycardia secondary to myxedema coma: case-report.

Myxedema coma occurs mostly in patients with long-standing untreated or undertreated hypothyroidism. Bradycardia is a well-known cardiac manifestation for myxedema coma; however, not all bradycardia with hypothyroidism are sinus bradycardia. Sick sinus syndrome is a group of arrhythmias caused by the malfunction of the natural pacemaker of the heart. Tachy-Brady syndrome is considered to be a type of sick sinus syndrome, where the heart alternates between tachycardia and bradycardia, and it is usually treated with pacemaker implantation along with rate slowing medical therapy. Here we report a case of an 83-year-old female who presented with myxedema coma and atrial fibrillation with tachycardia and intermittent slow ventricular response. We attempt to review the relationship between these two diseases and conclude that appropriate diagnosis of myxedema coma, may be beneficial in reducing the need for pacemaker implantation.

Neuroprotective Properties of Xenon.

Xenon is a rare noble gas that was introduced into clinical practice more than 70 years ago. Xenon's clinical properties are predicated by its ability to fit into preformed cavities of macromolecules thereby altering their biological functions. One such action targets the NMDA-subtype of the glutamate receptors thereby inhibiting its excitatory action. As the glutamate receptors are pivotal for both anesthesia and acute neurological injury, its clinical use has included both general anesthesia as well as neuroprotection. In this manuscript, the efficacy and safety of xenon in clinical trials that address both the anesthetic and neuroprotective applications are discussed. Because of the clinical safety of this chemically inert monatomic gas, the lack of an alternative for neuroprotection, and encouraging phase 2 trial data, a multinational pivotal randomized clinical trial (XePOHCAS) has been launched to assess the utility of xenon for patients that have been successfully resuscitated following an out of hospital cardiac arrest but still remain comatose, indicating ongoing neurological ischemic-perfusion injury. If successful, the trial will herald a new era of treatments for previously intractable conditions such as traumatic brain injury, ischemic and hemorrhagic strokes, and anesthetic-induced developmental neurotoxicity.

A clinical trial of enteral Levetiracetam for acute seizures in pediatric cerebral malaria.

BACKGROUND: Acute seizures are common in pediatric cerebral malaria (CM), but usual care with phenobarbital risks respiratory suppression. We undertook studies of enteral levetiracetam (eLVT) to evaluate pharmacokinetics (PK), safety and efficacy including an open-label, randomized controlled trial (RCT) comparing eLVT to phenobarbital. METHODS: Children 24-83 months old with CM were enrolled in an eLVT dose-finding study starting with standard dose (40 mg/kg load, then 30 mg/kg Q12 hours) titrated upward until seizure freedom was attained in 75% of subjects. The RCT that followed randomized children to eLVT vs. phenobarbital for acute seizures and compared the groups on minutes with seizures based upon continuous electroencephalogram. Due to safety concerns, midway through the study children allocated to phenobarbital received the drug only if they continued to have seizures (either clinically or electrographically) after benzodiazepine treatment. Secondary outcomes were treatment failure requiring cross over, coma duration and neurologic sequelae at discharge. PK and safety assessments were also undertaken. RESULTS: Among 30 comatose CM children, eLVT was rapidly absorbed and well-tolerated. eLVT clearance was lower in patients with higher admission serum creatinine (SCr), but overall PK parameters were similar to prior pediatric PK studies. Within 4 h of the first dose, 90% reached therapeutic levels (> 20 µg/mL) and all were above 6 µg/mL. 7/7 children achieved seizure freedom on the initial eLVT dose. Comparing 23 eLVT to 21 phenobarbital patients among whom 15/21 received phenobarbital, no differences were seen for minutes with seizure, seizure freedom, coma duration, neurologic sequelae or death, but eLVT was safer (p = 0.019). Phenobarbital was discontinued in 3/15 due to respiratory side effects. CONCLUSION: Enteral LVT offers an affordable option for seizure control in pediatric CM and is safer than phenobarbital. TRIAL REGISTRATION: NCT01660672 . NCT01982812 .