Featured new articles related to intranasal drug delivery
Baleine, J., C. Milesi, et al. (2014). "Intubation in the delivery room: experience with nasal midazolam." Early Hum Dev 90(1): 39-43.
Abstract: BACKGROUND: Neonates are often intubated in the delivery room (DR) without anesthesia because vascular access is impossible. AIMS: To assess neonatal comfort and adverse events after use of nasal midazolam (nMDZ) for intubation in the DR. STUDY DESIGN: Prospective data collection over 6months on the intubation of neonates with respiratory distress requiring tracheal instillation of surfactant. SUBJECTS: Twenty-seven neonates with median (Q25-75) gestational age and birthweight of, respectively, 29 (27-33)weeks and 1270 (817-1942)g received a 0.1mg/kg dose of nMDZ, and intubation was performed at the onset of tonus resolution or apnea. OUTCOME MEASURES: Comfort was assessed with a scale of hetero-pain assessment and electrical skin conductance monitoring. Continuous pulse oximetry was recorded in the first postnatal hour, with oscillometric blood pressure measurement every 10min. RESULTS: Seventy percent of the patients required a single dose, with intubation performed 4.8 (3-9)min after administration. Combined electro-clinical assessment found adequate comfort during the procedure in 68% of neonates. Mean blood pressure decreased from 39 (34-44)mmHg before to 31 (25-33)mmHg 1h following nMDZ (p=0.011). CONCLUSION: nMDZ provided rapid and effective sedation to intubate neonates in the DR but potentially exposed them to hypotension, thus requiring close hemodynamic monitoring.
Web site Editorial comments: This study is posted here simply to show that nasal drug delivery is effective and possible in neonates as young as 27 weeks gestational age.
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/24331827
Buonsenso, D., G. Barone, et al. (2014). "Utility of intranasal Ketamine and Midazolam to perform gastric aspirates in children: a double-blind, placebo controlled, randomized study." BMC Pediatr 14(1): 67.
Abstract: BACKGROUND: We performed a prospective, randomized, placebo-controlled study aimed to evaluate the efficacy and safety of a sedation protocol based on intranasal Ketamine and Midazolam (INKM) administered by a mucosal atomizer device in uncooperative children undergoing gastric aspirates for suspected tuberculosis. Primary outcome: evaluation of Modified Objective Pain Score (MOPS) reduction in children undergoing INKM compared to the placebo group. Secondary outcomes: evaluation of safety of INKM protocol, start time sedation effect, duration of sedation and evaluation of parents and doctors' satisfaction about the procedure. METHODS: In the sedation group, 19 children, mean age 41.5 months, received intranasal Midazolam (0.5 mg/kg) and Ketamine (2 mg/kg). In the placebo group, 17 children received normal saline solution twice in each nostril. The child's degree of sedation was scored using the MOPS. A questionnaire was designed to evaluate the parents' and doctors' opinions on the procedures of both groups. RESULTS: Fifty-seven gastric washings were performed in the sedation-group, while in the placebo-group we performed 51 gastric aspirates. The degree of sedation achieved by INMK enabled all procedures to be completed without additional drugs. The mean duration of sedation was 71.5 min. Mean MOPS was 3.5 (range 1-8) in the sedation-group, 7.2 (range 4-9) in the placebo-group (p <0.0001). The questionnaire revealed high levels of satisfaction by both doctors and parents in the sedation-group compared to the placebo-group. The only side effect registered was post-sedation agitation in 6 procedures in the sedation group (10.5%). CONCLUSIONS: Our experience suggests that atomized INKM makes gastric aspirates more acceptable and easy to perform in children. TRIAL REGISTRATION: Unique trial Number: UMIN000010623; Receipt Number: R000012422
Web site Editorial comments:
Here is a sedation study that used appropriate doses of nasal drugs (0.5 mg/kg of midazolam PLUS a sub-dissociative dose of nasal ketamine (2 mg/kg). This study highlights the fact that drug combinations are often better than single drugs depending on your clinical goal. In this case the patients received a dose of midazolam (0.5 mg/kg) proven to cause effective mild sedation in the majority of children, with a dose of ketamine that will have small sedative effects but strong analgesic effects and which will provide longer duration of effect. The result – highly effective sedation for over an hour duration that was safe and which resulted in high parental and physician satisfaction.
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/24598046
Wang, S. S., M. Z. Zhang, et al. (2014). "The sedative effects and the attenuation of cardiovascular and arousal responses during anesthesia induction and intubation in pediatric patients: a randomized comparison between two different doses of preoperative intranasal dexmedetomidine." Paediatr Anaesth 24(3): 275-281.
Abstract: OBJECTIVE: Premedication with intranasal dexmedetomidine (DEX) has shown to be an effective sedative in pediatric patients. This prospective, randomized, and controlled investigation was designed to evaluate whether the difference in intranasal DEX dosing would produce different beneficial effects on the attenuation of cardiovascular and arousal responses during anesthesia induction and intubation. METHODS: Forty children, aged from 3 to 6 years, of American Society of Anesthesiologists physical status I or II and scheduled for elective adenotonsillectomy randomly received intranasal DEX 1 mug.kg(-1) (group D1) or 2 mug.kg(-1) (group D2) 30 min before anesthesia induction. Anesthesia was induced with sevoflurane in oxygen flow. Mean arterial pressure (MAP) and heart rate (HR) as measurements of cardiovascular response and bispectral index (BIS) as an index of arousal response were recorded every 5 min after intranasal DEX administration and measured every 1 min for 5 min after intubation. Sedation status, behavior scores, and mask induction scores were also assessed. RESULTS: Mean arterial pressure did not show statistical differences during the anesthesia induction, but did demonstrate significantly milder responses to laryngoscopy and intubation in group D2 compared with group D1. Change in HR was consistent with MAP during laryngoscopy and intubation. Patients who received 2 mug.kg(-1) DEX presented with deeper sedation and less anxiety by the assessments of the alertness scale, behavior score, and BIS scores. Group D2 dosing achieved more favorable scores in children undergoing mask induction. CONCLUSION: Intranasal DEX 2 mug.kg(-1) administered 30 min before anesthesia induction provides considerable effect to attenuate the increase in MAP caused by intubation response. Changes in HR and BIS also demonstrate that this kind of premedication provides effective attenuation of intubation response. And preoperative intranasal DEX 2 mug.kg(-1) produces optimal-sedation, more favorable anesthesia induction course in pediatric patients. Premedication of intranasal DEX is a considerable way to blunt cardiovascular and arousal responses to endotracheal intubation.
Web site Editorial comments:
Here is a well designed RCT comparing intranasal dexmedetomidine at doses of 1 mcg/kg vs. 2 mcg/kg. The result show more blunting of cardiovascular responses and superior sedation to the higher dose. This is one of multiple studies that now confirm that 2 mcg/kg is likely the preferred dose of intranasal dexmedetomidine. Since this drug is soon to be generic, perhaps it will become the preferred intranasal sedation over midazolam and ketamine.Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/24224515
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