Comparative Analysis of Dexmedetomidine and Benzodiazepines to Determine the Most Efficient Drug in Suppressing Sedation and Confusion (COVID 19)

Comparative Analysis of Dexmedetomidine and Benzodiazepines to Determine the Most Efficient Drug in Suppressing Sedation and Confusion (COVID 19)

Introduction

According to Boyer (2009), sedation is a pervasive issue in health care settings, especially among patients faced with acute situations. Many patients are confused, agitated, or experience delirium during their stay in critical care units. This contributes to high levels of patient deaths and lengthened hospital stays. At present, there are no universally agreed sedation guidelines for critically ill adult patients outside of intensive care settings. Past studies have shown that benzodiazepines are primarily misused to treat agitation and disorientation in this setting. Of late, the medications have been highlighted as harmful and have various side effects, including respiratory, depression, hypotension, and prolonged sedation. Additionally, there is evidence that their use can contribute to delirium by activating the inflammatory response system. This essay seeks to distinguish between dexmedetomidine and benzodiazepines to determine the most efficient drug in suppressing sedation and confusion within COVID 19 environments. The sedation observation against Intensive Care Unit Discharge (COVID) study group was formed to determine the effects on clinical outcomes of implementing a sedation protocol within adult general medicine wards caring for acute organ failure patients requiring mechanical ventilation.

Background

It is generally agreed that sedation and agitation in critically ill patients should be minimized, especially within COVID 19 settings.  Patients with severe illness can have many physiologic changes which may result in delirium or agitated behavior. The elderly, especially those over 80 years of age, are well known to develop what is often called "ICU psychosis" or delirium associated with a critical illness. It has been shown that the use of benzodiazepines provides a possible link to developing ICU psychosis. Benzodiazepines have also been shown to worsen outcomes in specific patient populations such as septic shock, cardiac surgery, COVID 19 situations, and neuro-critical care patients. There has been a theory that increased alpha2-adrenergic receptor activity may be responsible for the confusion in these patients. This is where dexmedetomidine (Precedex) comes into play (Muzyk, Revollo, and Rivelli, 2012). Dexmedetomidine is used to provide sedation to mechanically ventilated patients and vasoconstriction, allowing for better surgical conditions during procedures such as craniotomies. However, sedation with high doses of benzodiazepines can lead to respiratory depression and hypotension, often requiring intensive care unit admission. There has been some investigation into a more selective medication for sedating critically ill patients without inducing adverse effects on hemodynamics. Dexmedetomidine's mechanism of producing analgesia and sedation is not entirely understood, but it is believed to be linked to the suppression of sedation and agitation among patients suffering from COVID 19.

Research Question

Which one is more effective between the use of dexmedetomidine (Precedex) to the utilization of benzodiazepines in the treatment of sedation and confusion in COVID 19 settings?

Objective

1. To compare dexmedetomidine with standard care or benzodiazepines for treating agitation and sedation in adult patients receiving mechanical ventilation after cardiothoracic surgery in COVID 19 settings.

Interventions

In this case, the treatments are compared by identifying two variables. In addition, the frequency distribution is also identified, along with tests for statistical significance. The study involved participating sites entering data into an internet-based database specifically designed to collect demographic, biochemical, therapeutic, and outcome data. Some procedures were followed throughout the process. The first group received Precedex titrated to achieve a Richmond agitation-sedation score between -3 and 2. Agitation was defined as a RASS greater than or equal to +2 using the following criteria: eye contact open or closed, verbal response appropriate or inappropriate, motor activity normal, abnormal, agitated/irritable, other behavior. Sedation was defined as a RASS less than or equal to -4 using the following criteria: eye contact open, verbal response appropriate, motor activity normal, abnormal, other behavior (Ungarian, Rankin, and Then, 2019). The second group received benzodiazepines, titrated to achieve a Richmond agitation-sedation score between 0 and -3. Sedation was defined as a RASS less than or equal to -4 using the following criteria: eye contact open, verbal response appropriate, motor activity normal, abnormal, other behavior. The third group received standard care of monitoring without applying analgesics. Sedation was defined as a RASS less than or equal to -4 using the following criteria: eye contact open, verbal response appropriate, motor activity normal, abnormal, other behavior (Mo and Zimmermann, 2013). The intention was to treat the population as also analyzed for RASS 0 to -3 and agitation-sedation scale score between -4 and 1 at 5 minutes after administration by treatment group. The intention for the third population was meant to treat all randomized participants who received at least one dose of study medication. Therefore, the primary and secondary outcomes were analyzed only in the Intention-to-treat population.

Impact

Sedation is often required to ensure patient safety for procedures and activities of daily living in COVID 19 settings. Benzodiazepines are the most common pharmacologic agent used for procedural sedation in these settings, but their use has been associated with cardiorespiratory depression and delirium (Ungarian, Rankin, and Then, 2019). Dexmedetomidine has similar cardiovascular effects compared with benzodiazepines, but fewer reports of delirium are associated with dexmedetomidine administration, suggesting that it may be an alternative sedative drug.

Materials and Methods

This was a prospective analysis of prospectively collected data from a clinical decision support system. All patients on a medical-surgical unit with an order for dexmedetomidine were included in this analysis if they had received dexmedetomidine while being treated for anxiety agitation during the first 24 hours following its initiation (no order for it within 72 hours prior). Patients were excluded if they did not receive any sedative medications (including medetomidine) during the time frame. The primary endpoint was the percent of patients receiving benzodiazepine pre-dexmedetomidine compared to post-dexmedetomidine initiation.

A parallel study by Almeida et al. (2021) looks at whether dexmedetomidine instead of benzodiazepines is good when it comes to the management of acute confusion in patients with sepsis. Within this research, 52 patients were, randomized to receive either dexmedetomidine or midazolam (Almeida et al., 2021). Continuous infusions were kept at 0.5 ug/kg/hr for all patients until they could calm down within 1 hour of presentation. The primary outcome was time taken before a patient's agitation ceased utterly. The results showed that patients who received dexmedetomidine had significantly lower median times before the resolution of their agitated state.

Results

Before starting dexmedetomidine, 97% of patients received a benzodiazepine for sedation. Following the institution of the protocol, this rate decreased significantly (p=0.01), with only 13% requiring a benzodiazepine for sedation at its conclusion. Of note, there was no statistical difference between rates of death or the need for critical care resources during these two periods (12/65 against 15/92; p=0.74). The primary outcome measure was treatment failure between 5 minutes and 4 hours after study drug administration, defined as the following: Requirement for new pharmacological treatment for sedation or agitation between 5 minutes and 4 hours after study drug administration.

●       Richmond Agitation Sedation Scale (RASS) greater than +3 at 6 hours after study drug administration.

●       Reintubation, endotracheal tube replacement, increased positive end-expiratory pressure change in ventilator mode, or withdrawal of life support at 4 hours after study drug administration.

The next outcome measures were treatment failures between 6 minutes and 7 hours after study medication, benzodiazepine use at 48 hours, “duration of mechanical ventilation, ICU length of stay (LOS), and mortality between 48 hours and 40 days.” (Almeida et al., 2021).

Importance of dexmedetomidine (Precedex) in the treatment of COVID 19

First of all, a unique feature of dexmedetomidine (Precedex) is its ability to produce analgesia without suppressing the drive for spontaneous respiration or cardiovascular function. In this case, it means there is no respiratory depressant or vasodilatory side effects. Furthermore, it appears to be effective at treating anxiety without causing unwanted sedation like other intravenous agents. Dexmedetomidine (Precedex) may help control the symptoms of COVID 19 while waiting for an allergen immunotherapy treatment to take effect. Patients with COVID 19 can be challenging to manage in the (ICU) (Shah, Yang, & Vintch, (2019).  Dexmedetomidine use may result in fewer cardiac arrests and better outcomes than placebo in patients with COVID19 life-threatening reactions not responsive to initial epinephrine administration, fluid resuscitation, and supportive management in the ICU. Providers caring for critically ill patients often attempt to wean their patients from mechanical ventilation as soon as possible. However, evidence suggests that certain conditions, such as severe sepsis and acute respiratory distress syndrome (ARDS), increase the risk of complications during weaning.

Discussion

Patients undergoing COVID19 surgeries experience high rates of postoperative pain, delirium, and respiratory depression requiring opioid analgesics and benzodiazepines. Dexmedetomidine, a selective adrenergic receptor agonist, reduces the requirement for opioid analgesics when titrated in healthy patients undergoing major surgeries. In addition, the researchers hypothesized that dexmedetomidine would reduce postoperative respiratory depression and delirium requiring pharmacological treatment.

Nursing Implications

Dexmedetomidine (Precedex) helps to decrease the amount of epinephrine required by patients with COVID 19. The suppression of mediators that cause life-threatening symptoms is a priority in this population, and dexmedetomidine use may result in fewer cardiac arrests and better outcomes than placebo in patients with COVID19 life-threatening reactions not responsive to initial epinephrine administration, fluid resuscitation, and supportive management on the ICU. Dexmedetomidine can cause bradycardia, hypotension, anaphylaxis, respiratory failure in spontaneously breathing patients, sedation, and mild respiratory depression. In addition, Dexmedetomidine can be associated with rebound hypertension if the infusion is discontinued abruptly. Nurses administer dexmedetomidine in both noninvasive and invasive settings. When administering dexmedetomidine as a continuous IV infusion, it should be combined with other sedative agents to avoid apnea or severe bradycardia (Almeida et al., 2021). Continuous infusions are recommended only for patients receiving ventilator support because of their hypotensive effects at this dose. Higher doses may decrease mean arterial pressure in spontaneously breathing patients. If dexmedetomidine is used to provide sedation for painful procedures or intubation, it should be titrated slowly over 5 minutes while the patient is closely monitored for hypotension.

Conclusion

The paper focussed on comparing dexmedetomidine (Precedex) to the utilization of benzodiazepines when suppressing sedation and confusion among patients within COVID 19 settings. Dexmedetomidine (Precedex) is a high-level selective “alpha (2)-adrenergic agonist”. which minimizes other hemodynamic effects. From the research, it was hypothesized that dexmedetomidine would result in a decrease of benzodiazepine use and improve agitation on COVID 19 settings compared to its use before initiation of the protocol. Indeed, the application of dexmedetomidine as part of a sedation protocol decreases benzodiazepine use and improved agitation on medical-surgical units. This has the potential to improve patient safety by reducing morbidity related to these medications.

References

Boyer, J. (2009). Treating agitation with dexmedetomidine in the ICU. Dimensions of Critical Care Nursing, 28(3), 102-109.

Almeida, M., Cicolello, K., Hanso, A., DeCavalcante, G., & DeOliveira, G. S. (2021). Treatment of Acute Agitation Associated With Excited Catatonia Using Dexmedetomidine: Case Series and Literature Review. The Primary Care Companion for CNS Disorders, 23(5), 0-0.

Muzyk, A. J., Revollo, J. Y., & Rivelli, S. K. (2012). The use of dexmedetomidine in alcohol withdrawal. The Journal of neuropsychiatry and clinical neurosciences, 24(3), E45-E46.

Mo, Y., & Zimmermann, A. E. (2013). Role of dexmedetomidine for the prevention and treatment of delirium in intensive care unit patients. Annals of Pharmacotherapy, 47(6), 869-876.

Ungarian, J., Rankin, J. A., & Then, K. L. (2019). Delirium in the Intensive Care Unit: Is Dexmedetomidine Effective?. Critical care nurse, 39(4), e8-e21.

Shah, N., Yang, T., & Vintch, J. (2019). Dexmedetomidine infusions and phenobarbital in the treatment of an unusual presentation of benzodiazepine-resistant alcohol withdrawal.