A new dosing protocol reduces dexmedetomidine-associated hypotension in critically ill surgical patients

Abstract

Background

Although no ideal sedative exists, dexmedetomidine is unique because it produces sedation and analgesia without decreasing the respiratory drive. Hemodynamic responses to dexmedetomidine are variable and dependent on the patient population. Our initial experience was associated with an unacceptable incidence of hypotension and bradycardia. We evaluated occurrence of hypotension and bradycardia in critically ill surgical patients receiving dexmedetomidine before and after implementation of a dosing protocol.

Methods

This is a retrospective chart review of all admissions to a university medical center–based, 44-bed surgical intensive care unit pre and post protocol implementation.

Results

Forty-four patients received dexmedetomidine including 19 historic controls and 25 dosed via protocol. Both groups had comparable demographics and initial and maximum dosages of dexmedetomidine. Use of the dosing protocol resulted in fewer dosage changes (mean ± standard deviation, 4.8 ± 3.8 compared to 7.8 ± 3.9; P = .014) and fewer episodes of hypotension (16% vs 68.4%; P = .0006) but did not influence bradycardic episodes (20% vs 15.5%; P > .99).

Conclusion

We found that use of a protocol that increases the time interval between dosage adjustments may reduce dexmedetomidine-associated hypotension.

Introduction

After publication of Too Err is Human: Building a Safer Health System in 1999 by the Institute of Medicine, medication safety has become a top priority in health care [1]. That report focused on the observation that many medical errors involve medications and concluded that health care providers need to design safer systems [2], [3]. Because of complexities of critical illness, patients in the intensive care unit (ICU) are considered to be at increased risk of medication errors and adverse drug events, particularly with intravenous medications [2], [3], [4], [5]. Proposed strategies to improve medication safety in the ICU include intensivist-lead, multidisciplinary rounds with pharmacist participation; standardized drug preparation and administration; computerized prescriber order entry; bar coding technology; computerized intravenous infusion devices; education; and developing a culture of safety [2], [6]. Because most medication errors and many adverse drug events are considered preventable, development of surveillance systems targeting strategies for improvement should help decrease adverse drug events in both the outpatient and the inpatient setting, including the ICU [6].

An essential part of ICU care is to protect patients from themselves during agitation, and this often requires use of sedatives such as propofol or benzodiazepines [7]. In addition, opioids are used to treat pain, a common contributor to agitation in surgical patients. Unfortunately, use of these medications is associated with adverse drug events such as respiratory depression, resulting in increased duration of mechanical ventilation, and development of ventilator-associated pneumonia, all of which increase ICU length of stay [8].

Dexmedetomidine is a sedative with a unique mechanism of action that became available in the United States in 1999 for sedation of critically ill patients [9]. Desirable properties of dexmedetomidine include induction of sedation and analgesia via stimulation of α₂-receptors without concomitant respiratory depression by γ-aminobutric acid-mimetic properties that accompany use of many other sedatives [9]. Additional advantages of dexmedetomidine include a relatively short half-life and hepatic metabolism [9]. Described adverse drug reactions with dexmedetomidine include altered blood pressure, nausea, and bradycardia [10], [11]. Hypotension, which is the most commonly reported adverse effect, results from a sympatholytic effect mediated by activation of central α_2a-receptors causing vasodilation [9], [12]. Thus, dexmedetomidine has the desirable characteristic of inducing sedation without causing respiratory depression, but it also has potential side effects that might preclude its use during critical illness.

Despite an initial enthusiasm for dexmedetomidine to treat agitation in our surgical ICU, data from our drug surveillance monitoring system suggested an unacceptable incidence of hypotension and bradycardia associated with its use. Closer evaluation revealed that hypotension often occurred when dexmedetomidine dosage was titrated rapidly (more frequently than every 20 minutes) compared with slower rates of titration [13]. Based upon these data, a dosing protocol for dexmedetomidine was developed that allows titration no more frequently than every 30 minutes. In this report, we described reduced occurrence of hypotension associated with dexmedetomidine in our surgical ICU after institution of this dosing protocol.