Cyclic Vomiting Syndrome in Pediatric Patients: A Review of Therapeutics

Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder that can present quite a challenge to clinicians caring for children with this complex disease. Different therapeutic interventions are recommended for prophylaxis and acute abortive therapy for a CVS attack. The aim of this review is to summarize therapeutic treatment recommendations from the 2008 North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHN) Consensus Statement on the Diagnosis and Management of Cyclic Vomiting Syndrome and discuss studies contemporary to this expert recommendation. After an extensive search of medical databases, 8 studies that evaluated therapeutic treatments for CVS were identified. Amitriptyline and cyproheptadine remain the standard of care for prophylaxis. Nutritional supplements such as carnitine and coenzyme Q10 have shown efficacy in decreasing episodes and severity in small studies with high tolerability among patients. The combination of ondansetron and sumatriptan are recommended for abortion of an acute vomiting episode, but other agents such as aprepitant and sedative agents can be considered when vomiting is refractory to initial treatments.

The Effect of Dexmedetomidine as a Sedative Agent for Mechanically Ventilated Patients With Sepsis: A Systematic Review and Meta-Analysis

Purpose: Dexmedetomidine has been shown to improve clinical outcomes in critically ill patients. However, its effect on septic patients remains controversial. Therefore, the purpose of this meta-analysis was to assess the effect of dexmedetomidine as a sedative agent for mechanically ventilated patients with sepsis.Methods: We searched PubMed, Embase, Scopus, and Cochrane Library from inception through May 2021 for randomized controlled trials that enrolled mechanically ventilated, adult septic patients comparing dexmedetomidine with other sedatives or placebo.Results: A total of nine studies involving 1,134 patients were included in our meta-analysis. The overall mortality (RR 0.97, 95%CI 0.82 to 1.13, P = 0.67, I2 = 25%), length of intensive care unit stay (MD −1.12, 95%CI −2.89 to 0.64, P = 0.21, I2 = 71%), incidence of delirium (RR 0.95, 95%CI 0.72 to 1.25, P = 0.70, I2 = 0%), and delirium free days (MD 1.76, 95%CI –0.94 to 4.47, P = 0.20, I2 = 80%) were not significantly different between dexmedetomidine and other sedative agents. Alternatively, the use of dexmedetomidine was associated with a significant reduction in the duration of mechanical ventilation (MD –0.53, 95%CI −0.85 to −0.21, P = 0.001, I2 = 0%) and inflammatory response (TNF-α: MD −5.27, 95%CI −7.99 to −2.54, P<0.001, I2 = 0%; IL-1β: MD −1.25, 95%CI −1.91 to –0.59, P<0.001, I2 = 0%).Conclusions: For patients with sepsis, the use of dexmedetomidine as compared with other sedative agents does not affect all-cause mortality, length of intensive care unit stay, the incidence of delirium, and delirium-free days. But the dexmedetomidine was associated with the reduced duration of mechanical ventilation and inflammatory response.

Trends in consultations for schizophrenia and non-affective psychoses in Italian emergency departments during and after the 2020 COVID-19 lockdown

Aims To analyse the hospital emergency department (HED) consultations for schizophrenia-spectrum disorders in nine Italian hospitals during the 2020 lockdown and post-lockdown periods, compared to the equivalent periods in 2019. Methods Characteristics of consultations, patients, and drug prescriptions were analysed. Joinpoint models were used to identify changes in the weekly trend of consultations. Results During the 2020 lockdown the overall number of HED consultations for schizophrenia decreased by 40.7% and after the lockdown by 12.2% compared with 2019. No difference was found in the proportion of consultations that led to GHPU admissions or compulsory admissions. Suicidality rates did not differ across the two years, with the exception of ideations and plans (+5.9%) during the post-lockdown period. We found an increase in benzodiazepine prescriptions in 2020 during the lockdown and post-lockdown periods (+10.6% and +20.8%, respectively), and a decrease of prescriptions for short-acting sedative agents in the post-lockdown period (-7.9%). An increase in the weekly trend of consultations occurred from March 11-17 (week 11) to June 26-June 30 (week 26). As a result, the initial gap in the number of consultations between the two years cancelled out at the end of June. Conclusions HED consultation rate for schizophrenia-spectrum disorders declined consistent with that of other psychiatric disorders. In the post-lockdown period the growth of suicidal ideation/planning and increase in the prescriptions of anxiolytic-sedating drugs may foreshadow that for some schizophrenia patients the exit from the lockdown period is not liberating, but rather a source of agitation or perturbation.

Practical Considerations for Dexmedetomidine Sedation in Adult Cataract Surgery Under Local/Regional Anesthesia: A Narrative Review

: Cataract surgery is predominantly performed under local/regional anesthesia, with or without sedation. The practice pattern of sedation is unknown and seems to vary significantly among institutions and countries, routinely administered in some parts of the world to the other extreme of none at all. The selection of sedative agents and techniques varies widely. Currently, there is no ideal sedative agent. Dexmedetomidine has gained recent attention for sedation in ophthalmic local/regional anesthesia due to its alleged advantages of effective sedation with minimal respiratory depression, decreased intraocular pressure, and reduced pain during the local anesthetic injection; however, they are subject to differing interpretations. Published literature also suggests that although dexmedetomidine sedation for cataract surgery under local/regional anesthesia is potentially useful, its role may be limited due to logistical difficulties in administering the recommended dose.

Comparison of different induction agents used for rapid sequence intubation

Securing the airway is the first step that clinicians take care of for clinically unstable patients. Rapid sequence intubation (RSI) has been reported by many clinicians to effectively achieve this. Many agents have been reported in the literature as effective induction agents for RSI. In this literature review, we have discussed the efficacies of the different induction agents that are commonly reported in the literature for RSI. Furthermore, RSI is done by paralytic and sedative agents that rapidly render the patient flaccid and unconscious to facilitate the emergent approaches to achieve successful tracheal intubation and minimize adverse events. We have discussed the efficacies and adverse events of benzodiazepines and barbiturates, ketamine, propofol, and etomidate. Each of these modalities has its advantages and adverse events, and clinicians should choose what is best for their patients based on the aforementioned discussion for each drug modality. We recommend that further investigations might be needed for further optimization of the induction agent and the relevant doses.

Review of the Physiology and Anesthetic Considerations for Pleuroscopy/Medical Thoracoscopy

Pleuroscopy or medical thoracoscopy is the second most common utilized procedure after bronchoscopy in the promising field of interventional pulmonology. Its main application is for the diagnosis and management of benign or malignant pleural effusions. Entry into the hemithorax is associated with pain and patient discomfort, whereas concurrently, notable pathophysiologic alterations occur. Therefore, frequently procedural sedation and analgesia is needed, not only to alleviate the patient’s emotional stress and discomfort by mitigating the anxiety and minimizing the pain but also for yielding better procedural conditions for the operator. The scope of this review is to present the physiologic derangements occurring in pleuroscopy and compare the various anesthetic techniques and sedative agents that are currently being used in this context.

Association Between Processed Electroencephalogram-Based Objectively Measured Depth of Sedation and Cerebrovascular Response: A Systematic Scoping Overview of the Human and Animal Literature

Background: Current understanding of the impact that sedative agents have on neurovascular coupling, cerebral blood flow (CBF) and cerebrovascular response remains uncertain. One confounding factor regarding the impact of sedative agents is the depth of sedation, which is often determined at the bedside using clinical examination scoring systems. Such systems do not objectively account for sedation depth at the neurovascular level. As the depth of sedation can impact CBF and cerebral metabolism, the need for objective assessments of sedation depth is key. This is particularly the case in traumatic brain injury (TBI), where emerging literature suggests that cerebrovascular dysfunction dominates the burden of physiological dysfunction. Processed electroencephalogram (EEG) entropy measures are one possible solution to objectively quantify depth of sedation. Such measures are widely employed within anesthesia and are easy to employ at the bedside. However, the association between such EEG measures and cerebrovascular response remains unclear. Thus, to improve our understanding of the relationship between objectively measured depth of sedation and cerebrovascular response, we performed a scoping review of the literature.Methods: A systematically conduced scoping review of the existing literature on objectively measured sedation depth and CBF/cerebrovascular response was performed, search multiple databases from inception to November 2020. All available literature was reviewed to assess the association between objective sedation depth [as measured through processed electroencephalogram (EEG)] and CBF/cerebral autoregulation.Results: A total of 13 articles, 12 on adult humans and 1 on animal models, were identified. Initiation of sedation was found to decrease processed EEG entropy and CBF/cerebrovascular response measures. However, after this initial drop in values there is a wide range of responses in CBF seen. There were limited statistically reproduceable associations between processed EEG and CBF/cerebrovascular response. The literature body remains heterogeneous in both pathological states studied and sedative agent utilized, limiting the strength of conclusions that can be made.Conclusions: Conclusions about sedation depth, neurovascular coupling, CBF, and cerebrovascular response are limited. Much further work is required to outline the impact of sedation on neurovascular coupling.

Safety and Complications of Sedation Anesthesia during Pediatric Auditory Brainstem Response Testing

<b><i>Objective:</i></b> The auditory brainstem response (ABR) test has been widely used in childhood. Although it is a painless procedure, sedation can be needed in pediatric patients. Thus, this study aimed to evaluate safety and complications of sedation anesthesia applied in pediatric patients during ABR testing. <b><i>Methods:</i></b> Medical records of 75 children who underwent ABR testing between 2018 and 2020 were evaluated retrospectively in terms of applicability, safety, and complications of sedation anesthesia. <b><i>Results:</i></b> The ages ranged from 3 to 9 (mean 6.2) years. Comorbidity was detected in 20% (<i>n</i> = 15); 3 had multiple comorbidities, and the most common comorbidity was Down syndrome (4%). The drugs used in sedation anesthesia were midazolam in 81.3% (<i>n</i> = 61), a combination of propofol and ketamine in 14.7% (<i>n</i> = 11), and only propofol in 4% (<i>n</i> = 3) of the patients. An additional drug use was needed in 44% (<i>n</i> = 33). The mean procedure time was 40 (range 30–55) min. The mean anesthesia duration was 45 (range 35–60) min. The mean recovery time was 10 (range 5–15) min. Complications related to anesthesia developed in 4 (5.33%) of the patients; respiratory distress, agitation, cough, and nausea-vomiting were seen in one of the patients, respectively. Complications like bradycardia and respiratory or cardiac arrest were not seen at all. <b><i>Conclusions:</i></b> The complication rate of sedation anesthesia performed during ABR testing of pediatric patients is quite low. It may be more beneficial to use combinations of sedation drugs instead of using a single sedation drug. Although sedation anesthesia appears to be safe in general, the potentially life-threatening complications of sedative agents should be remembered, especially in children who have comorbidities.

Diagnosis of acute poisoning by addictive and psychotropic substances based on the toxidrome

Background. Poisoning by addictive and psychotropic substances is one of the main reasons for the admission of patients to emergency departments in most countries of the world. The purpose of this study was to investigate the current structure of toxic syndromes in patients with acute poisoning and to analyze existing approaches to the diagnosis of addictive and psychotropic substance poisoning based on the syndromic approach. Materials and methods. Medical data of 2987 patients treated with the diagnosis: “Acute drug poisoning” (ICD-10: T40.0-T40.3) in the Kyiv Toxicological Center were studied. Laboratory studies of addictive and psychotropic substances in the biological environment were performed using immunochromatographic analysis (rapid tests) and chromate-mass spectrometry (device Aligent 6850/5973N, column HP-5MS). Statistical analysis was performed using the program Statistica 12.6 (Windows 10/7). Results. According to the Center for Mental Health and Monitoring of Drugs and Alcohol of the Ministry of Health of Ukraine in 2018, the most common substances that result in abuse were: alcohol — 14.6 %, cannabis — 2.8 %, opioids — 2.1 %, sedative agents — 1.1 %, solvents — 0.9 %, amphetamine-type stimulants — 0.2 %, cocaine — 0.1 %, and hallucinogens — 0.1 %. The range of substances that caused severe poisoning in adults in 2016–2020 represented by: ethanol — 29.2 %, opioids — 42.3 %, cannabinoids — 8.4 %, sedative agents and hypnotics — 9.5 %, cocaine, and stimulants, inclu-ding caffeine — 7.4 %, hallucinogens — 5.5 %, solvents — 2.1 %. The following toxidromes were diagnosed: sedative in 46.3 % of patients, opioid — 37.6 %, sympathomimetic — 17.7 %, anticholinergic — 9.5 %, serotonin — 0.4 %, and syndrome of inappropriate diuretic hormone secretion (SIADH) — 0.2 %. During the study period, the number of combined poisonings increased 1.8 times (from 20.5 to 37.1 %), and among the combinations of addictive and psychotropic substances, the most common are methadone + ethanol, methadone + benzodiazepines, methadone + amphetamine, opioids + cocaine + ethanol, opioids + cannabis, as well as other combinations involving methamphetamine, hallucinogens, analgesics. Clinical diagnosis of combined poisonings is difficult, miosis may be absent in tramadol and meperidine poisoning, in cases of combined use of opioids and stimulants, or extremely severe cases, when the patient shows signs of deep post-hypoxic encephalopathy. Modern synthetic opioids (fentanyl and buprenorphine analogues) significantly outweigh the toxic effects of heroin, so there is a fairly common approach to using higher initial doses of naloxone in the treatment of such overdoses. However, approaches to the use of naloxone differ in various scientific sources. The practical experience in the Kyiv Toxicological Center proves that treatment can be started with standard doses of naloxone and quickly increased in the absence of side effects (agitation, convulsions, pulmonary edema). Given the fact that modern test systems are aimed at finding a small range of narcotic and psychotropic substances and do not determine their concentration, considerable attention should be paid to clinical diagnosis based on the definition of pathological symptoms and syndromes. Since the main target for narcotic and psychotropic substances is the nervous system, the identification of biomarkers of its dysfunction at different levels is key in the diagnosis of poisoning. Based on certain biomarkers, an understanding of the existing toxic syndrome (toxidrome) is formed. Today, opioids play a key role in morbidity and mortality from drug poisoning in Ukraine. A threatening trend in recent years is the increase in the proportion of combined poisonings by opioids and other substances, which complicates the determination of the toxidrome. It is important to note that the “fashion” for the use of combinations of narcotic drugs and psychotropic substances among drug users is constantly changing, so doctors try to regularly update information on available drugs and psychotropic substances in the region, which are popular among consumers and characteristic manifestations of poisoning. The universal approach ABCDE should be used in cases where there are no specific tests for toxic substances, and because more than a third of positive tests show the presence of two or more xenobiotics. Conclusions. Identification of toxidrome is important from the standpoint of diagnosis and treatment of acute poisoning. Many researchers note that its importance exceeds the value of rapid tests to determine the toxic substance, and the patient’s vital signs and careful examination are the best clues for choosing treatment tactics. In cases of combined poisoning with drugs or psychotropic substances, or in situations where it is not possible to conduct rapid testing of the patient’s urine for toxic substances, it is necessary to approach the use of antidotes (naloxone) with caution. It is important to remember that the object of medical intervention in any poisoning is the patient, not the toxin or the results of laboratory tests, which do not always correctly indicate the poison. Pharmacological interventions in the treatment of a patient with acute addictive or psychotropic substance poisoning should be aimed at correcting the underlying pathological syndrome (if possible), taking into account not to exacerbate its manifestations, but rather to minimize its severity and duration.

An Overview of the Biological Activity of Pyrrolo[3,4-c]pyridine Derivatives

Pyrrolo[3,4-c]pyridine is one of the six structural isomers of the bicyclic ring system containing a pyrrole moiety fused to a pyridine nucleus. The broad spectrum of pharmacological properties of pyrrolo[3,4-c]pyridine derivatives is the main reason for developing new compounds containing this scaffold. This review presents studies on the biological activity of pyrrolo[3,4-c]pyridines that have been reported in the scientific literature. Most of these derivatives have been studied as analgesic and sedative agents. Biological investigations have shown that pyrrolo[3,4-c]pyridines can be used to treat diseases of the nervous and immune systems. Their antidiabetic, antimycobacterial, antiviral, and antitumor activities also have been found.