5 Clinical Trials for Various Conditions
This intervention pilot feasibility study will assess the impact of auricular acupressure as an additional non-pharmacologic therapy for infants at risk for developing Iatrogenic Withdrawal Syndrome (IWS) in the Pediatric Cardiac Intensive Care Unit (PCICU) of Monroe Carrell Jr Children's Hospital at Vanderbilt (MCJCHV). The investigators will recruit 40 healthy, 34 weeks gestational age or older infants exposed to prolonged medications (greater than 5 days) for cardiac procedures that may cause withdrawal upon cessation such as opioids, benzodiazepines, or other sedative medications. Participants will receive the auricular acupressure in addition to the standard of care such as clustered nursing care, touch, position change, environmental controls, holding, and swaddling.
Withdrawal from opioids and sedatives administered for medical purposes (i.e. iatrogenic withdrawal) often goes unrecognized in the critically ill, but its prevalence is high. Reports describing what is being implemented at the bedside to prevent iatrogenic withdrawal are lacking, and how patients are monitored and assessed for withdrawal has not been adequately studied. Therefore, the investigators overall objective is to determine the current analgesia and sedation weaning practices in adult ICUs. In order to accomplish this objective the investigators plan to conduct a prospective, observational, point prevalence trial. Data from this project will help support future investigation of iatrogenic withdrawal.
The analgesic and sedation requirements in critically ill patients with COVID-19 have yet to be described. There are various factors that are likely affecting the agents being utilized for analgesia and sedation in these patients with little evidence to guide therapy. In addition, such non-evidence based practice may be leading to an increased incidence of iatrogenic withdrawal. The investigators seek to determine the analgesia and sedation requirements in critically ill patients with COVID-19 and report practice patterns that may be associated with iatrogenic withdrawal in these patients. The contribution of the proposed research will be an understanding of current analgesia and sedation use and weaning in critically ill patients with COVID-19, and practice patterns that may indicate the occurrence of iatrogenic withdrawal. This contribution will be significant because it will determine how analgesics and sedatives are being utilized in critically ill patients with COVID-19, and how their use may be leading to additional morbidity. Data from this initial trial will help support further research on the actual incidence of iatrogenic withdrawal in this patient population. Together such research will help inform practice patterns and therapy recommendations in advance of the next SARS-related outbreak.
Thousands of critically ill infants (and children) are exposed to opioids and benzodiazepines to achieve sedation and analgesia as part of routine care in neonatal and pediatric intensive care units. While the use of these agents are undisputedly beneficial in reducing pain and anxiety, improving ventilation, reducing pulmonary vascular resistance and improving outcomes; the consequence is often the development of tolerance and physiologic dependence - similar to prenatal exposure from these same classes of drugs. The investigators have recently reported the results of randomized placebo control trial showing that the addition of clonidine (central alpha 2 agonist) to tapering doses of opioids was efficacious and safe in treating opioid dependence in infants who had moderate to severe neonatal abstinence syndrome from prenatal drug exposure to opioids. Currently, the investigators propose to perform a double-blind, randomized placebo control trial in a cohort of critically ill infants without prenatal drug exposure at Johns Hopkins Hospital to test the overall hypothesis that early addition of clonidine to a cohort of critically ill neonates on mechanical ventilation who are receiving opioids and benzodiazepines for analgesia and sedation will be efficacious and safe in reducing both the incidence and severity of withdrawal symptoms (NICU-NAS); as well as, reducing the time to complete sedative and analgesic drug detoxification. The hypothesis will be tested by addressing 2 specific aims that will determine: 1) the efficacy and safety of clonidine in critically ill infants, and 2) pharmacokinetics and pharmacodynamics using population-based pharmacokinetics in this vulnerable infant population who have only been exposed to these drugs as part of their routine care. Many "standard of care practices" are incorporated in neonatal and pediatric care prior to evidence based studies. This proposal will fill a much needed gap in translating what the investigators have learned about basic mechanisms mediating dependence and withdrawal to proven therapies for vulnerable pediatric populations.
The purpose of this study is to determine if administering methadone to mechanically ventilated patients in the medical intensive care unit (ICU) requiring continuous infusions of sedatives and analgesics will decrease the time of mechanical ventilation, when initiated within 48 hours of their admission. Patients meeting enrollment criteria will be randomly assigned to receive methadone or placebo in addition to standard care. Methadone is a long acting pain medication that is approved by the Food and Drug Administration (FDA) to manage withdrawal from opioids and moderate to severe pain. Both of these indications are a frequent concern for critically ill patients that require mechanical ventilation. These patients often require intravenous (IV) opioids to manage the pain they experience due to their illness, procedures, and mechanical ventilation. During this time patients can develop physical dependence, which leads to withdrawal symptoms when the opioids are stopped or the dose is reduced. These symptoms can include agitation, pain, diarrhea and several others. Currently this is managed by a slow reduction in the dose of the IV opioid, but this can lead to prolonged time on mechanical ventilation, which has been associated with increased morbidity. Administering oral methadone to patients experiencing withdrawal symptoms has been shown to reduce and even eliminate these symptoms in the outpatient setting. This should also benefit patients in the ICU experiencing withdrawal from intravenous opioids required during their stay. It may allow for the other opioids to be discontinued more quickly, allowing for a shorter duration of mechanical ventilation. The level of pain and sedation will be assessed between groups randomized to either methadone or placebo in addition to current intravenous sedative and analgesic agents. The duration of mechanical ventilation will be assessed between both groups. Opioid withdrawal symptoms may manifest or be mistaken for delirium symptoms. ICU delirium is often managed with antipsychotic medications. To assess if methadone can reduce the need for antipsychotic medication, all administered antipsychotic doses will be recorded and total consumption will be compared between the two groups. Methadone has been associated with abnormal heart rhythms in rare instances. To ensure patient safety, data from the heart monitor will be collected and compared between the two groups to assess for QT interval prolongation.