Deciphering the host genetic factors conferring susceptibility to severe COVID-19 using exome sequencing.

The COVID-19 pandemic remains a significant public health concern despite the new vaccines and therapeutics. The clinical course of acute SARS-CoV-2 infection is highly variable and influenced by several factors related to the virus and the host. Numerous genetic studies, including candidate gene, exome, and genome sequencing studies, genome-wide association studies, and other omics efforts, have proposed various Mendelian and non-Mendelian associations with COVID-19 course. In this study, we conducted whole-exome sequencing on 90 unvaccinated patients from Turkey with no known comorbidities associated with severe COVID-19. Of these patients, 30 had severe, 30 had moderate, and 30 had mild/asymptomatic disease. We identified rare variants in genes associated with SARS-CoV-2 susceptibility and pathogenesis, with an emphasis on genes related to the regulation of inflammation, and discussed these in the context of the clinical course of the patients. In addition, we compared the frequencies of common variants between each group. Even though no variant remained statistically significant after correction for multiple testing, we observed that certain previously associated genes and variants showed significant associations before correction. Our study contributes to the existing literature regarding the genetic susceptibility to SARS-CoV-2. Future studies would be beneficial characterizing the host genetic properties in different populations.

Quantitative Electroencephalography Analysis for Improved Assessment of Consciousness Levels in Deep Coma Patients Using a Proposed Stimulus Stage.

"Coma" is defined as an inability to obey commands, to speak, or to open the eyes. So, a coma is a state of unarousable unconsciousness. In a clinical setting, the ability to respond to a command is often used to infer consciousness. Evaluation of the patient's level of consciousness (LeOC) is important for neurological evaluation. The Glasgow Coma Scale (GCS) is the most widely used and popular scoring system for neurological evaluation and is used to assess a patient's level of consciousness. The aim of this study is the evaluation of GCSs with an objective approach based on numerical results. So, EEG signals were recorded from 39 patients in a coma state with a new procedure proposed by us in a deep coma state (GCS: between 3 and 8). The EEG signals were divided into four sub-bands as alpha, beta, delta, and theta, and their power spectral density was calculated. As a result of power spectral analysis, 10 different features were extracted from EEG signals in the time and frequency domains. The features were statistically analyzed to differentiate the different LeOC and to relate with the GCS. Additionally, some machine learning algorithms have been used to measure the performance of the features for distinguishing patients with different GCSs in a deep coma. This study demonstrated that GCS 3 and GCS 8 patients were classified from other levels of consciousness in terms of decreased theta activity. To the best of our knowledge, this is the first study to classify patients in a deep coma (GCS between 3 and 8) with 96.44% classification performance.

Cytokine Levels and Severity of Illness Scoring Systems to Predict Mortality in COVID-19 Infection.

Various scoring systems and cytokines have been cited as predicting disease severity in COVID-19 infection. This study analyzed the link between mortality rate, levels of cytokines, and scoring systems such as the Glasgow Coma Scale (GCS), Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Charlson Comorbidity Index in patients infected with COVID-19. Adult patients infected with COVID-19 were followed up in the intensive care unit (ICU) and analyzed prospectively. We measured serum cytokine levels (Interleukin-10 (IL-10), Interleukin-8 (IL-8), Interleukin-6 (IL-6), Interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α) and High mobility group box 1 (HMGB-1)) and recorded GCS, APACHE II, SOFA, and Charlson comorbidity index scores on admission to the ICU. Receiver operating curve (ROC) analysis was performed to predict mortality from IL-1ß, IL-6 IL-10, IL-8, TNF-α, and HMGB-1 values. Study participants were grouped as follows: Group A, survivors, and Group B, deceased, during the 28-day follow-up. The mean age was 65.69 (±13.56) in Group A (n = 36) and 70.85 (±10.06) in Group B (n = 27). The female/male ratio was 23/40. Age, sex, body mass index (BMI), comorbid illnesses, GCS, APACHE II, SOFA, and Charlson scores, duration of hospitalization or ICU admission, therapeutic choices, and lymphocyte, PMNL, NLR, platelet, D-dimer, fibrinogen, GGT, CRP, procalcitonin, and lactate levels were similar between the groups. The frequency of acute kidney injury (AKI) was higher in Group B (p = 0.005). Serum IL-10, IL-8, IL-6, IL-1ß, TNF-α, HMGB-1, ferritin, and LDH values were higher, and PaO2/FiO2 was lower in Group B than in Group A. ROC analysis showed that there was an association between serum IL-1ß (>1015.7), serum IL-6 (>116.7), serum IL-8 (>258.4), serum IL-10 (>247.5), serum TNF-α (>280.7), and serum HMGB-1 (>23.5) and mortality. AKI gave rise to a greater risk of mortality (odds ratio: 7.081, p = 0.014). Mortality was associated with serum IL-10, IL-8, IL-6, IL-1ß, TNF-α, and HMGB-1 but not with GCS, APACHE II, SOFA, or Charlson comorbidity index scores. AKI increased the risk of mortality by seven times. Our findings suggest that cytokine levels (serum IL-10, IL-8, IL-6, IL-1ß, TNF-α, and HMGB-1) were predictors of mortality in COVID-19 infection. In addition, our results might give an opinion about the course of COVID-19 infection.

The Clinical and Laboratory Efficacy of HA 330 Treatment Combined with Continuous Renal Replacement Therapy in Septic Shock Patients: A Case Series.

INTRODUCTION: Blood purification therapy is a method used to enable cytokine removal and to improve disturbed immune homeostasis in patients with sepsis or septic shock. This study aimed to evaluate the impact of HA 330 treatment on biochemical and hemodynamic parameters and cytokine levels in adult patients with septic shock. METHODS: Critically ill patients with septic shock who received continuous veno-venous hemodiafiltration and HA 330 treatment were included in this prospective observational study. Biochemical and hemodynamic parameters were followed throughout HA 330 treatment. Serum interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α, high-mobility group box1 (HMGB-1) protein, IL-10 levels were analyzed by ELISA method, before and after each HA 330 session. RESULTS: A total of 18 critically ill patients were included in this study. The median APACHE 2 score was 22.2 ± 7.49 and median SOFA score 9.6 ± 5.44 on intensive care unit admission. SOFA scores were significantly decreased on the 3rd day of HA 330 treatment, compared to 2nd day scores (p = 0.017). Median leukocyte value was significantly decreased (p = 0.027 and p = 0.024), while hemodynamic parameters remained unchanged throughout the HA 330 treatment. Median CRP and procalcitonin levels were significantly reduced at day 3 of HA 330 treatment compared to the baseline (p = 0.015 and p = 0.033, respectively). Serum IL-1 ß, IL-6, IL-8, TNF-a, HMGB-1, and IL-10 levels decreased insignificantly by 11.5%, 26.4%, 11.4%, 37.9%, 0.02%, and 35.5%, respectively, at the end of the hemoperfusion treatment compared to the pre-treatment. CONCLUSION: The administration of HA 330-based hemoperfusion in septic shock patients revealed improvements in SOFA scores, leukocyte count, and CRP and procalcitonin levels. However, there was no statistically significant change in concentrations of inflammatory cytokines and hemodynamic parameters during HA 330 treatment.

Gastric ultrasound, citrulline, and intestinal fatty acid-binding protein as markers of gastrointestinal dysfunction in critically ill patients: A pilot prospective cohort study.

BACKGROUND: Gastrointestinal (GI) dysfunction is common in the intensive care unit (ICU), although there is no consensus on biomarkers of GI dysfunction. We aimed to evaluate ultrasound-based gastric antrum measurements and serum intestinal fatty acid-binding protein (IFABP) and citrulline levels in relation to GI dysfunction in critically ill patients. METHODS: Adult critically ill patients receiving enteral nutrition and stayed for in the ICU for ≥48 h was included. GI dysfunction was described using Gastrointestinal Dysfunction Score (GIDS). Gastric antrum measurements, including craniocaudal (CC) diameter, anteroposterior diameter, and antral-cross sectional area (CSA), as well as serum levels for IFABP and citrulline, were prospectively recorded at baseline and on day 3 and day 5 of enteral nutrition. The receiver operating characteristic (ROC) analysis was performed to evaluate gastric ultrasound parameters, serum IFABP, and citrulline concentrations in predicting GI dysfunction. RESULTS: Thirty-nine participants with a median age of 60 years were recruited and 46.2% of participants had GI dysfunction. ROC analysis revealed that the cutoff value of CSA score to predict GI dysfunction was 4.48 cm2 , which provided 72.7% sensitivity and 77.2% specificity (area under the curve = 0.768, 95% CI: 0.555-0.980). At baseline, gastric residual volume was highly correlated with CC diameter and CSA (r = 0.764, P < 0.001 and r = 0.675, P < 0.001, respectively). Serum IFABP and citrulline levels had no correlation with GI dysfunction or gastric ultrasound parameters (P > 0.05). CONCLUSION: CSA was associated with GI dysfunction in critically ill patients. Serum IFABP and citrulline concentrations were poor in predicting GI dysfunction.

New Avenues to Explore in SARS-CoV-2 Infection: Both TRIM25 and TRIM56 Positively Correlate with VEGF, GAS6, and sAXL in COVID-19 Patients.

The ongoing COVID-19 pandemic poses a significant threat to human health. Many hypotheses regarding pathogenesis have been proposed and are being tried to be clarified by experimental and clinical studies. This study aimed to reveal the roles of the innate immune system modulator GAS6/sAXL pathway, endothelial dysfunction markers vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1α, and antiviral effective TRIM25 and TRIM56 proteins in pathogenesis of COVID-19. The study included 55 patients with COVID-19 and 25 healthy individuals. The serum levels of GAS6, sAXL, VEGF, HIF-1α, TRIM25, and TRIM56 were measured using commercial ELISA kits and differences between COVID-19 patients and healthy controls, and the relationship to severity and prognosis were evaluated. GAS6, sAXL, TRIM56, and VEGF were found to be higher, while TRIM25 was lower in patients. There were strong positive correlations between GAS6, sAXL, TRIM25, TRIM56, and VEGF. None of the research parameters other than HIF-1α was associated with severity or prognosis. However, HIF-1α was positively correlated with APACHE II. We speculate that the antiviral effective TRIM25 and TRIM56 proteins, as well as the GAS6/sAXL pathway, act together as a defense mechanism in COVID-19. We hope that our study will contribute to further studies to elucidate the molecular mechanism associated with TRIM56, TRIM25, GAS6, sAXL, and VEGF in COVID-19 patients.

Classification of Depth of Coma Using Complexity Measures and Nonlinear Features of Electroencephalogram Signals.

In recent years, some electrophysiological analysis methods of consciousness have been proposed. Most of these studies are based on visual interpretation or statistical analysis, and there is hardly any work classifying the level of consciousness in a deep coma. In this study, we perform an analysis of electroencephalography complexity measures by quantifying features efficiency in differentiating patients in different consciousness levels. Several measures of complexity have been proposed to quantify the complexity of signals. Our aim is to lay the foundation of a system that will objectively define the level of consciousness by performing a complexity analysis of Electroencephalogram (EEG) signals. Therefore, a nonlinear analysis of EEG signals obtained with a recording scheme proposed by us from 39 patients with Glasgow Coma Scale (GCS) between 3 and 8 was performed. Various entropy values (approximate entropy, permutation entropy, etc.) obtained from different algorithms, Hjorth parameters, Lempel-Ziv complexity and Kolmogorov complexity values were extracted from the signals as features. The features were analyzed statistically and the success of features in classifying different levels of consciousness was measured by various classifiers. Consequently, levels of consciousness in deep coma (GCS between 3 and 8) were classified with an accuracy of 90.3%. To the authors' best knowledge, this is the first demonstration of the discriminative nonlinear features extracted from tactile and auditory stimuli EEG signals in distinguishing different GCSs of comatose patients.

Analysis of Consciousness Level Using Galvanic Skin Response during Therapeutic Effect.

The neurological status of patients in the Intensive Care Units (ICU) is determined by the Glasgow Coma Scale (GCS). Patients in coma are thought to be unaware of what is happening around them. However, many studies show that the family plays an important role in the recovery of the patient and is a great emotional resource. In this study, Galvanic Skin Response (GSR) signals were analyzed from 31 patients with low consciousness levels between GCS 3 and 8 to determine relationship between consciousness level and GSR signals as a new approach. The effect of family and nurse on unconscious patients was investigated by GSR signals recorded with a new proposed protocol. The signals were recorded during conversation and touching of the patient by the nurse and their families. According to numerical results, the level of consciousness can be separated using GSR signals. Also, it was found that family and nurse had statistically significant effects on the patient. Patients with GCS 3,4, and 5 were considered to have low level of consciousness, while patients with GCS 6,7, and 8 were considered to have high level of consciousness. According to our results, it is obtained lower GSR amplitude in low GCS (3, 4, 5) compared to high GCS (7, 8). It was concluded that these patients were aware of therapeutic affect although they were unconscious. During the classification stage of this study, the class imbalance problem, which is common in medical diagnosis, was solved using Synthetic Minority Over-Sampling Technique (SMOTE), Adaptive Synthetic Sampling (ADASYN) and random oversampling methods. In addition, level of consciousness was classified with 92.7% success using various decision tree algorithms. Random Forest was the method which provides higher accuracy compared to all other methods. The obtained results showed that GSR signal analysis recorded in different stages gives very successful GCS score classification performance according to literature studies.

Effects of Dexmedetomidine Infusion During Sevoflurane Anesthesia on Otoacoustic Emissions.

BACKGROUND AND OBJECTIVES: Knowing the ototoxic potential of the agents used in medical treatments is important for the protection of hearing. Although we have knowledge regarding some effects of dexmedetomidine, which is an anesthetic-sparing drug, its influence over the hearing system has never been studied and is obscure yet. The aim of this study is to determine the effects of intravenous dexmedetomidine application during sevoflurane anesthesia on otoacoustic emissions (OAEs). SUBJECT AND METHODS: This prospective randomized study was performed on 60 patients (34 male, 26 female, mean age: 30.6±9.2 years) who were scheduled for an elective surgery under general anesthesia and the patients were enrolled and randomly divided into 2 groups. They received dexmedetomidine (Group D) or Saline (Group S) infusion during a standardized Sevoflurane anesthesia. Transient and distortion product OAEs were measured preoperatively and postoperatively (24th hour). OAE results were compared within and between groups. RESULTS: In group D postoperative OAEs were lower than preoperative OAEs and postoperative levels of group S, especially at low frequencies (p<0.05). CONCLUSIONS: Dexmedetomidine infusion affects the micromechanical function of cochlea especially in the low-frequency region. Dexmedetomidine should be carefully used during general anesthesia to avoid its probable harmful effects on cochlear micromechanics.

Sedation for paediatric transcatheter atrial septal defect closure: comparison of two sedation protocols.

AIM: This study aimed to compare the effects of dexmedetomidine-propofol and ketamine-propofol sedation on haemodynamic stability, immobility, and recovery time in children who underwent transcatheter closure of atrial septal defects. METHODS: In all, 46 children scheduled for transcatheter closure of atrial septal defects (n = 46) were included. The dexmedetomidine-propofol group (n = 23) received dexmedetomidine (1 µg/kg) and propofol (1 mg/kg) for induction, followed by dexmedetomidine (0.5 µg/kg/hour) and propofol (100 µg/kg/minute) for maintenance. The ketamine-propofol group (n = 23) received ketamine (1 mg/kg) and propofol (1 mg/kg) for induction, followed by ketamine (1 mg/kg) and propofol (100 µg/kg/minute) for maintenance. RESULTS: In all, 11 patients in the dexmedetomidine group (47.8%) and one patient (4.3%) in the ketamine group demonstrated a decrease ≥20% from the baseline in mean arterial pressure (p = 0.01). Heart rates decreased ≥20% from the baseline value in 10 patients (43.4%) in the dexmedetomidine group and three patients (13%) in the ketamine group (p = 0.047). Heart rate values were observed to be lower in the dexmedetomidine group throughout the procedure after the first 10 minutes. The number of patients requiring additional propofol was higher in the dexmedetomidine group (p = 0.01). The recovery times were similar in the two groups--15.86 ± 6.50 minutes in the dexmedetomidine group and 19.65 ± 8.19 minutes in the ketamine group; p = 0.09. CONCLUSION: The ketamine-propofol combination was less likely to induce haemodynamic instability, with no significant change in recovery times, compared with the dexmedetomidine-propofol combination. The ketamine-propofol combination provided good conditions for the intervention.

The effects of dexmedetomidine added to spinal levobupivacaine for transurethral endoscopic surgery.

BACKGROUND: Intrathecal α2 agonists prolong the duration of action of local anesthetics and reduce the required dose. Dexmedetomidine is an α2 receptor agonist and its α2/α1 selectivity is 8 times higher than that of clonidine. AIMS: In this study, we aimed to investigate the effect of adding dexmedetomidine to intrathecal levobupivacaine on the onset time and duration of motor and sensory blocks. STUDY DESIGN: Randomized controlled study. METHODS: Patients were randomly assigned into two groups. Group L (n= 30) patients received 3 mL (15 mg) of 0.5% levobupivacaine +0.3 mL normal saline and Group LD (n= 30) patients received 3 mL (15 mg) of 0.5% levobupivacaine + 0.3 mL (3 µg) dexmedetomidine. Sensory block onset time, block reaching time to T10 dermatome, the most elevated dermatome level, two dermatome regression time, sensory block complete regression time as well as motor block onset time, reaching Bromage 3 and regressing to Bromage 0 were recorded. RESULTS: Sensory and motor block onset times were shorter in Group LD than in Group L (p<0.001). The regression of the sensory block to S1 dermatome and Bromage 0 were longer in Group LD than Group L (p<0.001). The two dermatome regression time was longer in Group LD than Group L (p< 0.001). There were no statistically significant differences between groups in blood pressure and heart rate. There was no statistically significant difference between groups when adverse effects were compared. CONCLUSION: We conclude that intrathecal dexmedetomidine addition to levobupivacaine for spinal anaesthesia shortens sensory and motor block onset time and prolongs block duration without any significant adverse effects.

Characteristics of acute adult poisonings in a university hospital emergency department in central Turkey: a three-year analysis.

OBJECTIVE: To evaluate the etiologic and demographic characteristics of acute adult poisoning cases and to obtain up-to-date information on acute poisonings. METHODS: A retrospective study was conducted to evaluate 1254 adults who presented with acute poisoning to the Emergency Department of our tertiary care university hospital in central Turkey from January 2007 to December 2009. The data extracted from each chart related to age, gender, marital status, agent involved in the poisoning, season of event, route of poisoning, time between ingestion or exposure and arrival at the casualty ward, mechanism of toxic exposure (unintentional or intentional), level of consciousness, length of stay in the ward, and outcome. RESULTS: Acute poisonings comprised 1.40% of Emergency Department patients; 65% were female, while 47% were between the ages of 16 and 25 years. Medicinal drugs were the most common cause of poisonings (68%), followed by gases (9.5%). Antidepressants were the most frequent drug ingested (18%), followed by analgesics (16%). Intentional poisonings constituted the majority of cases (78%). Most suicide attempts were made by women (68%) and majority of the patients were married (57%). Twenty patients (1.6%) died during their hospital stay, with organophosphate pesticides being the most common agent (n = 8) involved in fatal poisonings. CONCLUSION: Pharmaceutical agents, carbon monoxide and pesticides are the three most common poisoning agents. Deliberate self-poisoning is common in adults in the area of the study; the risk being highest in females and younger adults. These up-to-date data provide important information on the characteristics of acute poisonings and can guide activities such as professional training, preventive measures, community education and new research.

Is the addition of dexmedetomidine to a ketamine-propofol combination in pediatric cardiac catheterization sedation useful?

Pediatric patients undergoing cardiac catheterization usually need deep sedation. In this study, 60 children were randomly allocated to receive sedation with either a ketamine-propofol combination (KP group, n = 30) or a ketamine-propofol-dexmedetomidine combination (KPD group, n = 30). Both groups received 1 mg/kg of ketamine and 1 mg/kg of propofol for induction of sedation, and the KPD group received an additional 1 µg/kg of dexmedetomidine infusion during 5 min for induction of sedation and a maintenance infusion of 0.5 µg/kg/h. In both groups, 0.2 mg/kg of propofol was administered as a bolus to maintain a Ramsey sedation score (RSS) greater than 4 throughout the procedure. None of the patients in either group required intubation. In the KP group, one patient required mask ventilation. The chin-lift maneuver needed to be performed for eight patients in the KP group and one patient in the KPD group (p < 0.05). Adding dexmedetomidine to the ketamine-propofol combination decreased movement during the procedures. The heart rate in the KPD group was significantly lower after induction of sedation and throughout the procedure (p < 0.05). No significant differences in systolic blood pressure, diastolic blood pressure, or respiration rates were found between the two groups (p > 0.05). The mean recovery time was longer in the KP group (5.86 vs 3.13 min; p < 0.05). Adding dexmedetomidine to a ketamine-propofol combination led to a reduced need for airway intervention and to decreased movement during local anesthetic infiltration and throughout the procedure. The recovery time was shorter and hemodynamic stability good in the KPD group.

Dexmedetomidine vs midazolam for premedication of pediatric patients undergoing anesthesia.

BACKGROUND: Dexmedetomidine, an α(2)-receptor agonist, provides sedation, analgesia, and anxiolytic effects, and these properties make it a potentially useful anesthetic premedication. In this study, we compared the effects of intranasal dexmedetomidine and midazolam on mask induction and preoperative sedation in pediatric patients. METHODS: Ninety children classified as ASA physical status I, aged between 2 and 9, who were scheduled to undergo an elective adenotonsillectomy, were enrolled for a prospective, randomized, and double-blind controlled trial. All of the children received intranasal medication approximately 45-60 min before the induction of anesthesia. Group M (n = 45) received 0.2 mg·kg(-1) of intranasal midazolam, and Group D (n = 45) received 1 µg·kg(-1) of intranasal dexmedetomidine. All of the patients were anesthetized with nitrous oxide, oxygen, and sevoflurane, administered via a face mask. The primary end point was satisfactory mask induction, and the secondary end points included satisfactory sedation upon separation from parents, hemodynamic change, postoperative analgesia, and agitation score at emergence. RESULTS: Satisfactory mask induction was achieved by 82.2% of Group M and 60% of Group D (P = 0.01). There was no evidence of a difference between the groups in either sedation score (P = 0.36) or anxiety score (P = 0.56) upon separation from parents. The number of patients who required postoperative analgesia was higher in the midazolam group (P = 0.045). CONCLUSION: Intranasal dexmedetomidine and midazolam are equally effective in decreasing anxiety upon separation from parents; however, midazolam is superior in providing satisfactory conditions during mask induction.

Changing pattern of antibiotic susceptibility in intensive care units: ten years experience of a university hospital.

The study was performed to assess microorganisms and antibiotic susceptibility patterns during ten years in intensive care units of a University Hospital. Infection Control Committee has active, prospective surveillance in ICUs for thirteen years. Ten years data of ICUs was evaluated retrospectively from surveillance forms. Microorganisms and their antibiotic resistance were recorded according to the years. During ten years, gram negative microorganisms were the most frequent isolated microorganisms from clinical specimens. Acinetobacter baumannii (21.8%), Pseudomonas aerigunosa (16%), Escherichia coli (10.4%) and Klebsiella pneumoniae (8%) were the most common gram negative microorganisms. However, Staphylococcus aureus was the most prevalent gram positive microorganism, the incidence decreased from 18.6% to 4.8% during ten years. Also antibiotic susceptibility of microorganisms changed during ten years. Carbapenem resistance increased from 44% to 92% in A. baumannii and ciprofloxacin resistance increased in E. coli from 28% to 60% and in K. pneumoniae from 21% to 55% during ten years. However, methicilin resistance decreased in S. aureus from 96% to 54%. In conclusion, antibiotic resistance is growing problem in ICUs. Rationale antibiotic policies and infection control measures will prevent the development of resistance.

The comparison of the effects of dexmedetomidine and midazolam sedation on electroencephalography in pediatric patients with febrile convulsion.

BACKGROUND: When electroencephalogram (EEG) activity is recorded for diagnostic purposes, the effects of sedative drugs on EEG activity should be minimal. This study compares the sedative efficacy and EEG effects of dexmedetomidine and midazolam. SUBJECTS AND METHODS: EEG recordings of 60 pediatric subjects with a history of simple febrile convulsions were performed during physiologic sleep. All of these patients required sedation to obtain follow-up (control) EEGs. Subjects in Group D received 0.5 µg·kg(-1) of dexmedetomidine, and those in Group M received 0.1 mg·kg(-1) of midazolam. For rescue sedation, the same doses were repeated to maintain a Ramsey sedation score level of between 4 and 6. RESULTS: The mean doses that were required for sedation were 0.76 µg·kg(-1) of dexmedetomidine and 0.38 mg·kg(-1) of midazolam. Diastolic blood pressure and HR were lower in Group D than in Group M (P < 0.05). Hypoxia was observed in 11 (36.7%) subjects in Group M and none in Group D; this was statistically significant (P < 0.001). Frontal and parieto-occipital (PO) EEG frequencies were similar during physiologic sleep and dexmedetomidine sedation. However, EEG frequencies in these areas (P < 0.001) and PO EEG amplitude (P = 0.030) were greater during midazolam sedation than during physiologic sleep. CONCLUSIONS: Dexmedetomidine is a suitable agent to provide sedation for EEG recording in children. There is less change in EEG peak frequency and amplitude after dexmedetomidine than after midazolam sedation.

Dexmedetomidine added to levobupivacaine prolongs axillary brachial plexus block.

BACKGROUND AND OBJECTIVES: We evaluated the effect of adding dexmedetomidine to levobupivacaine for axillary brachial plexus blockade. The primary endpoints were the onset and duration of sensory and motor block and duration of analgesia. METHODS: Sixty patients scheduled for elective forearm and hand surgery were divided into 2 equal groups in a randomized, double-blind fashion. The 4 main nerves in the axilla (musculocutaneus, radial, median, ulnar) were identified using neural stimulation. Patients were assigned randomly to 1 of the 2 groups. In group L (n = 30), 40 mL (200 mg) of 0.5% levobupivacaine + 1 mL saline and in group LD (n = 30), 40 mL (200 mg) of 0.5% levobupivacaine + 1 mL dexmedetomidine were given. Motor and sensory block onset times, block durations, and duration of analgesia were recorded. RESULTS: Demographic data and surgical characteristics were similar in both groups. Sensory and motor block onset times were shorter in group LD than in group L (P < 0.05). Sensory and motor blockade durations were longer in group LD than in group L (P < 0.01). Duration of analgesia was longer in group LD than in group L (P < 0.05). Systolic arterial blood pressure levels in group LD at 10, 15, 30, 45, 60, 90, and 120 minutes were significantly lower than those in group L (P < 0.05). Diastolic arterial blood pressure levels in group LD at 60, 90, and 120 minutes were significantly lower than those in group L (P < 0.05). Heart rate levels in group LD, except basal measurements, were significantly lower than those in group L (P < 0.05). In group LD bradycardia was observed in 7 patients, although there was no bradycardia in group L (P < 0.05). CONCLUSIONS: Dexmedetomidine added to levobupivacaine for axillary brachial plexus block shortens the onset time and prolongs the duration of the block and the duration of postoperative analgesia. However, dexmedetomidine also may lead to bradycardia.

The effects of caudal or intravenous clonidine on postoperative analgesia produced by caudal levobupivacaine in children.

BACKGROUND: Clonidine is used increasingly in pediatric anesthesia practice to prolong the duration of action of caudal block with a local anesthetic agent. Which route of administration of clonidine is the most beneficial remains unknown. We compared the effects of caudal and intravenous clonidine on postoperative analgesia produced by caudal levobupivacaine. METHODS: Sixty ASA I and II children, aged 2-8 undergoing inguinal hernia repair or orchidopexy surgery received standardized premedication with midazolam and general anesthesia. The children were randomized in a double-blind fashion to three groups. Group L (n = 20) patients received 0.75 ml x kg(-1) of caudal 0.25% levobupivacaine and i.v. 5 ml saline, Group L-Ccau (n = 20) patients received 0.75 ml x kg(-1) of caudal 0.25% levobupivacaine + 2 microg x kg(-1) clonidine and i.v. 5 ml saline, Group L-Civ (n = 20) patients received 0.75 ml x kg(-1) of caudal 0.25% levobupivacaine and i.v. 2 microg x kg(-1) clonidine in 5 ml of saline. Mean arterial blood pressure, heart rate, peripheral oxygen saturation, and end-tidal carbon dioxide values were recorded. Postoperative pain [Children and Infants Postoperative Pain Scale (CHIPPS) score], sedation (Ramsay Sedation Scale) and motor blockade (Modified Bromage Scale) were assessed at predetermined time points during the first 24 h after surgery. RESULTS: Caudal clonidine significantly delayed the time to first rescue analgesic and fewer patients required rescue analgesia in the 24 h after surgery. No motor block was observed in any of the three groups on awakening or during the study period. In Group L-Ccau, the CHIPPS score was lower than in Group L at all times through 240 min (P < 0.05), while the pain scores were lower in Group L-Civ only at extubation and at 240 min (P < 0.05). CONCLUSIONS: Caudal clonidine prolongs the duration of analgesia produced by caudal levobupivacaine without causing significant side effects and this is because of a spinal mode of action.

Comparison of 0.5% levobupivacaine, 0.5% bupivacaine, and 2% lidocaine for retrobulbar anesthesia in vitreoretinal surgery.

PURPOSE: The authors compared the efficacy of local anesthetics levobupivacaine, bupivacaine, and lidocaine for retrobulbar anesthesia in vitreoretinal surgery. METHODS: A total of 135 patients presenting for vitreoretinal surgery under local anesthesia were included in the study. Patients were randomly allocated to one of three groups. Group LB patients received 5 mL of 0.5% levobupivacaine, Group L patients received 5 mL of 2% lidocaine, and Group B patients received 5 mL of 0.5% bupivacaine for retrobulbar anesthesia via inferotemporal injection. Sensory and motor block durations were recorded. Intraoperative and postoperative pain was assessed by using verbal pain scala. Anesthesia efficiency, patient and surgeon satisfaction, and akinesia were assessed by using point scales. Hemodynamic data and adverse events were recorded. RESULTS: The demographic characteristics of patients, duration of surgery, and hemodynamic data in both groups were similar. The duration of motor and sensory block was longer in levobupivacaine and bupivacaine groups than lidocaine group. Pain on injection was found more frequent in Group L and Group B than Group LB and the difference between the Groups LB and B was significant (p<0.05). Surgeon and patient satisfaction were also higher and intraoperative pain was less in levobupivacaine group than lidocaine and bupivacaine groups. CONCLUSIONS: Levobupivacaine provides longer motor and sensory block duration and higher surgeon and patient satisfaction than lidocaine and bupivacaine when used for retrobulbar anesthesia in vitreoretinal surgery.

Comparison between dexmedetomidine and midazolam for sedation of eclampsia patients in the intensive care unit.

PURPOSE: This study compares the effectiveness of midazolam and dexmedetomidine for the sedation of eclampsia patients admitted to our intensive care unit (ICU). PATIENTS AND METHODS: Forty women with eclampsia requiring termination of pregnancy by caesarean delivery were randomized in to 2 groups of 20 to receive either midazolam or dexmedetomidine. The midazolam group received a loading dose of 0.05 mg/kg followed by an infusion of 0.1 mg kg(-1) h(-1). The dexmedetomidine group loading dose was 1 microg/kg per 20 minutes, followed by continuous infusion at 0.7 microg kg(-1) h(-1). Heart rate, blood pressure, Ramsey sedation score, antihypertensive need, convulsion fits, and duration in ICU were monitored and recorded all through the ICU stay. RESULTS: Dexmedetomidine markedly reduced heart rates for the first 24 hours (P < .05) compared with midazolam, but there were no differences at 48 and 72 hours. Mean arterial blood pressures were similar in the 2 groups (P > .05), although in the dexmedetomidine group, it was lower at 5, 6, 12, and 24 hours compared with the first 4 hours (P < .05). Moreover, fewer patients given dexmedetomidine required nitroglycerine and nitroprusside (P < .05). The duration of ICU stay was less in the dexmedetomidine group, 45.5 hours (range, 15-118 hours), than in the midazolam group, 83 hours (minimum-maximum, 15-312 hours). CONCLUSION: Dexmedetomidine sedation in eclampsia patients is effective in reducing the demand for antihypertensive medicine and duration of ICU stay.