Comparison of Intranasal Midazolam with Oral Midazolam for Premedication in Children

INTRODUCTION: Surgery and anaesthesia induce considerable emotional stress and psychological consequences in children. This stress may remain in the child’s psyche long after the hospital experience has passed, and it was first described by Duputyren in 1834. Age, parental anxiety level, previous hospital experiences and type of surgery are factors that can influence a child’s anxiety level and psychological well being. Preoperative anxiety stimulates sympathetic, parasympathetic and endocrine system leading to an increase in heart rate, blood pressure and cardiac excitability. These reactions reflect the child’s; • fear of separation from parents and home environment. • fear of physical harm. • fear of unfamiliar routines. • fear of surgical instruments and procedures. The preoperative interventions directed towards reduction of anxiety can be grouped into psychological and pharmacological methods. The introduction of new drugs and alternative routes of administration like transmucosal route in last decade by avoiding painful intramuscular injections, the most horrifying experience for a child, has facilitated a more rational approach to premedication for paediatric patients. In paediatric anaesthesia, premedication needs to be in an acceptable form, to have a rapid onset with minimal hangover effect and without side effects. Midazolam, a sedative with all the desirable properties of a benzodiazepine was introduced into clinical practice in 1980s. Midazolam, a water soluble benzodiazepine, may be administered by various routes. Oral and rectal routes are used widely and provide effective sedation. However, there are concerns about the wide bioavailability when given by these routes , ranging from 18% to 44% with an appreciable first pass effect. Intramuscular administration is painful and the sublingual route has poor compliance. The intranasal route for midazolam has been used since 1988 and has the advantage of rapid absorption directly into the systemic circulation with no first pass effect and a bio- availability of 55-83% Intranasal midazolam is absorbed from an area rich in blood supply and avoids the disadvantage of passing through the portal circulation, thus increasing the bio-availability of the drug. Tolerance to midazolam is good, and the duration of action is shorter and more predictable than other benzodiazepines. Intranasal midazolam has all the advantages of intravenous administration without the disadvantages of pain and fear associated with intramuscular and intravenous injections. AIM OF THE STUDY: The aim of the study is to compare the effectiveness of Intranasal and oral midazolam used as a premedication in paediatric patients undergoing minor elective surgical procedures. MATERIALS AND METHODS: Seventy paediatric patients belonging to ASA physical status I and II scheduled for elective minor surgical procedures were included in the study. Children belonged to age group of 2 to 8 years of both sexes. The children were randomly allocated into 2 groups with 35 patients in each group. (Group N and Group O). It was a comparative study. The study was approved by the Institutional Ethical Committee and parents provided written informed consent before premedication of their children. Inclusion Criteria: 1. ASA I and II physical status, 2. Age group 2-8 yrs, 3. weight < 20 kgs. Exclusion Criteria: 1. ASA III and IV, 2. Nasal Infection, 3. Nasal Pathology, 4. Nasal Allergy and URI, 5. Children with Seizure disorder, 6. History of adverse reactions to benzodiazepines, 7. patient taking other sedative drugs. MATERIALS 1. Nasal midazolam spray (Insed atomiser), 2. Oral midazolam. Preparation of the Patient: Written informed consent from the parent obtained. All patients fasted as per NPO guidelines. Demographic data including age, weight and sex of the children were recorded. The children were given premedication 30 minutes before surgery orally or nasally. The reaction of the children to the premedication was noted. SUMMARY: We compared the efficacy of midazolam as a paediatric premedication when used in two different routes. Midazolam was used as premedication in intranasal and oral routes in children undergoing minor surgical procedures and the efficacy of the drug in producing preoperative sedation, anxiolysis and cooperation during separation from the parents, venepuncture and face mask application was compared using separate scoring systems. The following observations were made during the study. There are no significant differences between the two groups in demographic data. The time of onset of sedation is 8.42 minutes with intranasal midazolam and 15.82 minutes with oral midazolam. We observed that intranasal midazolam has more rapid onset of action compared to oral midazolam, which is statistically significant. The sedation scores are better with intranasal midazolam than oral midazolam at 10 minutes, 20 minutes and30 minutes which are statistically significant. The anxiolysis is better with nasal midazolam group with statistical significance. There is no significant difference in the co-operation score for venepuncture, separation from the parents and mask application between the two groups. No patient was oversedated or drowsy postoperatively. No complications were observed in both the groups. CONCLUSION: In conclusion, Intranasal midazolam when used as a premedication in children, in a dose of 0.2 mg/kg has more rapid onset of action with satisfactory sedation and anxiolysis than oral midazolam. The rapid onset of action of nasal midazolam makes it an ideal route for premedication in children

Profile of Children Ventilated in Paediatric Intensive Care Unit of a Tertiary Care Hospital

INTRODUCTION: Ventilatory support is an essential and a common form of therapy in Pediatric Critical Care Unit. In recent years, this modality has evolved into a highly specialized discipline (1). The term mechanical ventilation refers to various artificial means used to support ventilation and oxygenation (2). Natural spontaneous ventilation occurs when the respiratory muscles (diaphragm, intercostal muscles) create negative intrathoracic pressure, in part by expanding the rib cage, leading to lung expansion, which pulls air into the alveoli and allows gas exchange to occur. In contrast, ventilation is achieved in intubated patients by delivering compressed gas to the lungs by positive pressure ventilation. During positive pressure ventilation, the flow of gas during inspiration and expiration is driven by the airway pressure gradient between the airway opening and the alveoli. During inspiration, the airway opening pressure is greater than alveolar pressure, thereby driving gas into the lungs and inflating them. Expiration is usually passive and occurs because, at the end of inspiration, alveolar pressure becomes greater than airway pressure. AIM OF THE STUDY: To study the etiological and clinical profile of children ventilated in PICU and various complications and outcome of these children. DISCUSSION: This descriptive observational study was conducted to study the demographic, clinical profile of children who were ventilated at the PICU, and their complications and outcome. The commonest indication for intubation and artificial ventilation was circulatory dysfunction including shock, unlike other studies,where neurological indications predominated in the study by Kendirli et al and respiratory causes were the commonest causes for artificial ventilation in the study by Indrajit et al. Intubation was performed orotracheally in 97.9% of children and nasotracheally in 2.1% in present study compared to no nasotracheal intubation performed in the study by Da Silva et al. Rapid Sequence intubation(RSI) was performed in 54.8% of the study population compared to routine RSI protocol used in the study by Da Silva et al. Though mechanical ventilation is the standard of care, our hospital being a Government hospital and a tertiary referral centre, many critically ill children with need for ventilation are being referred to here, which could not be met by the available resources in PICU and hence, many children needed manual ventilation. Out of the 106 children who were manually ventilated, 45 (42.5%) survived. Another 75 children required manual ventilation for varying duration in addition to mechanical ventilation, and the survival was 52.1% in that subgroup. None of the studies in available literature have data on manual ventilation. The mean duration of artificial ventilation in the study was 3.56±5.2 days. The duration of mechanical ventilation in the study was 4.6±5.9 days. A total of 181 children (96.3%) were ventilated manually during their PICU stay, and among them, 75 children were ventilated mechanically after variable duration of manual ventilation. In comparison, the ventilation days were 18.8±14.1 days in the study by Kendirli et al and the median ventilation days were 6.5 days in the study by Da Silva et al. SUMMARY AND CONCLUSIONS: 1. Infants contributed 46.3% of children who were ventilated in the Pediatric Intensive Care Unit. 2. The sex ratio was almost equal with slight male preponderance. Male:Female = 1.09:1.0 3. The commonest cause for intubation was circulatory failure and the commonest clinical diagnosis was septic shock. 4. Of the children who were ventilated in the PICU, 76.6% were intubated at the Emergency Department. 5. Rapid Sequence Intubation was performed in 54.8% of children, and orotracheal route was the commonest route of intubation. • Many children (56.4%) were manually ventilated and it was associated with an increased risk of mortality especially when done for 48 hours or more. 6. Nosocomial pneumonia was the commonest complication encountered in ventilated children and was more common in those who were reintubated. 7. Mortality and complications in ventilated children in the PICU can be reduced with increased availability of mechanical ventilators

Quality assessment of commercial formulations of tin based herbal drug by physico-chemical fingerprints

The Tin based herbal drug Vanga Parpam is extensively used for treating urino genital infections, Odema, Polydepsia and Dyspepsia effectively. There are no reports of physico chemical fingerprints for the tin based drug available. Proper characterization techniques are required for checking the quality of the commercial samples, in terms of the physical and chemical constitution to meet the expected criteria to support its use worldwide. Two popular commercial brands such drug were characterized and compared in terms of morphology, composition, crystal lattice, and oxidation state of the active metal. Physico-chemical fingerprints were generated for the samples using analytical techniques like Powder X ray crystallography, Scanning Electron Microscopy, Energy Dispersive X ray Analysis and Inductively Coupled Plasma Optical Emission Spectroscopy and Fourier Transformed Infra Red spectroscopy. It was found that the percentage of tin varied drastically in both brands along with a difference in the percentage composition of other elements and surface morphology which would have significant impact on the therapeutic efficacy and pharmacological activity of the drug samples. The current study appropriately substantiated the need for the use of modern analytical techniques in the establishment of quality and safety assurance of such potent drug

Choosing project risk management techniques. A theoretical framework

The pressure for increasing quality while reducing time and costs places particular emphasis on managing risk in projects. To this end, several models and techniques have been developed in literature and applied in practice, so that there is a strong need for clarifying when and how each of them should be used. At the same time, knowledge about risk management is becoming of paramount importance to effectively deal with the complexity of projects. However, communication and knowledge creation are not easy tasks, especially when dealing with uncertainty, because decision-making is often fragmented and a comprehensive perspective on the goals, opportunities, and threats of a project is missing. With the purpose of providing guidelines for the selection of risk techniques taking into account the most relevant aspects characterising the managerial and operational scenario of a project, a theoretical framework to classify these techniques is proposed. Based on a literature review of the criteria to categorise risk techniques, three dimensions are defined: the phase of the risk management process, the phase of the project life cycle, and the corporate maturity towards risk. The taxonomy is then applied to a wide selection of risk techniques according to their documented applications. This work helps to integrate the risk management and the knowledge management processes. Future research efforts will be directed towards refining the framework and testing it in multiple industrie

Predictors of Response to Hydroxyurea and Switch to Ruxolitinib in HU-Resistant Polycythaemia VERA Patients: A Real-World PV-NET Study

In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), the predictors of response, and patients' triggers for switching to ruxolitinib are uncertain. In a real-world analysis, we evaluated the predictors of response, their impact on the clinical outcomes of CR to HU, and the correlations between partial or no response (PR/NR) and a patient switching to ruxolitinib. Among 563 PV patients receiving HU for ≥12 months, 166 (29.5%) achieved CR, 264 achieved PR, and 133 achieved NR. In a multivariate analysis, the absence of splenomegaly (p = 0.03), pruritus (p = 0.002), and a median HU dose of ≥1 g/day (p &lt; 0.001) remained associated with CR. Adverse events were more frequent with a median HU dose of ≥1 g/day. Overall, 283 PR/NR patients (71.3%) continued HU, and 114 switched to ruxolitinib. In the 449 patients receiving only HU, rates of thrombosis, hemorrhages, progression, and overall survival were comparable among the CR, PR, and NR groups. Many PV patients received underdosed HU, leading to lower CR and toxicity rates. In addition, many patients continued HU despite a PR/NR; however, splenomegaly and other symptoms were the main drivers of an early switch. Better HU management, standardization of the criteria for and timing of responses to HU, and adequate intervention in poor responders should be advised

A Study of Marine Incidents Databases in the Baltic Sea Region

A comprehensive risk analysis makes use of different datasets. Marine incidents data are essentially important datasets. The purpose of this study is to analyse marine incident databases in the BSR (Baltic Sea Region). The marine incident data in the region are inhabited by a wide rage of issues, such as limited data accessibility and availability, and the diversity in data quality, structure, amount, accuracy, degree of detail and languages. Preparing for the data analysis is a very cumbersome, labour intensive, time consuming and expensive process. Merging different datasets from different countries into a single dataset is a very difficult process, if not impossible for a complete data merging. The paper provides experiences on how to overcome some of these issues and proposes some suggestions for improvements in the future