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Clinical Investigation

Weaning Dexmedetomidine in Non-ICU Areas: An Implementation Effort

Solodiuk, Jean C. RN, CPNP, PhD1; Sweet, Erin RN, MSN, FNP-C1; Greco, Christine MD1; Manzi, Shannon F. PharmD, BCPP2; Giangregorio, Maeve MSN, RN, CPN, NE-BC2; Homoki, Adam MSN, BA, RN, NE-BC2; Li, Liza PharmD, BCPS, BCPPS2; Mansfield, Laura MD3; Mahoney, Judy MSN, RN, NE-BC2; Kleinman, Monica E. MD4

Author Information
Pediatric Critical Care Medicine: May 2022 - Volume 23 - Issue 5 - p 353-360
doi: 10.1097/PCC.0000000000002889
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Abstract

RESEARCH IN CONTEXT

  • Protocolized weaning of sedatives such as dexmedetomidine in non-ICU areas is feasible and can be accomplished safely even among pediatric patients at high risk for withdrawal using standardized weaning guidelines and a dedicated team.
  • At our institution, implementation of guidelines was associated with reduced ICU length of stay for patients recovering from critical illness.

Critically ill, mechanically ventilated children require sedation for both comfort and safety. Prolonged administration of sedatives, including dexmedetomidine, is associated with the development of tolerance and iatrogenic withdrawal syndrome when sedatives are abruptly discontinued or weaned too quickly (1). Iatrogenic withdrawal syndrome occurs frequently (2), is uncomfortable (3), and is associated with increased morbidity and hospital costs (4). Dexmedetomidine is advantageous in that it may mitigate alternative sedative needs (5–7). The propensity for dexmedetomidine withdrawal is highest in critically ill patients who receive prolonged infusions. Safe weaning to mitigate dexmedetomidine withdrawal may prolong ICU length of stay. Although withdrawal secondary to prolonged use has previously been described (7–12), an effective weaning process has yet to be well described.

Based on the well-described benefits of protocolizing opioid and benzodiazepine weaning (13,14), the primary aim of this effort was to develop and implement clinical practice guidelines for weaning dexmedetomidine in children recovering from critical illness. The secondary aim was to reduce ICU length of stay. These outcomes were chosen for their relevance to daily practice. The intended audience is physicians, nurses, and pharmacists caring for hospitalized children weaning from dexmedetomidine used for sedation during their critical phase of illness.

METHODS

This development and implementation of clinical guidelines effort was approved by the institutional review board (IRB) at Boston Children’s Hospital (IRB-P00033751) with a waiver of consent. It is a collaboration between the Divisions of Pain Medicine and Critical Care Medicine and the Pharmacy and Nursing Departments. We report this development and implementation effort using the Appraisal of Guidelines for Research and Evaluation checklist (15).

This effort took place within a 404-bed quaternary pediatric center with a medical-surgical, a medical, and a cardiovascular ICUs totaling 83 beds. A select workgroup used the Population/patient/problem-Intervention-Comparator-Outcome (PICO) framework to formulate a structured literature review. To identify relevant articles, MEDLINE was searched using search terms: dexmedetomidine, wean, pediatrics, withdraw, assessment on published studies from January 1, 2012, to December 31, 2017 (Table 1). Titles and abstracts were screened for studies on weaning and withdrawal in children. Articles focusing on sedation and topics other than the PICO questions were excluded. The initial guidelines were based both on available evidence and clinical experience. The guidelines were revised several times over a 6-month period by an interdisciplinary taskforce including physicians, bedside nurses, and pharmacists from the ICUs, physicians, and nurse practitioners from the pain service, and nursing leadership and bedside nurses in non-ICU areas. Final consensus on guideline formulation was reached after collaboration and discussion amongst the interdisciplinary taskforce before implementation. The guideline is reviewed at least every 3 years per hospital policy or more often as needed. In addition, weaning measures are reviewed quarterly by the hospital’s pain interdisciplinary committee and any challenges or issues are discussed at that time.

TABLE 1. - Population/Patient/Problem-Intervention-Comparator-Outcome Questions
PICO Category Questions
P Patient Critically ill children recovering from critical illness
Population Variations in practice related to weaning patients from dexmedetomidine
Problem
I Intervention What are the signs and symptoms of dexmedetomidine withdrawal?
What tools measure dexmedetomidine withdrawal?
How fast can dexmedetomidine be safely weaned?
What are the risk factors for dexmedetomidine withdrawal including (days of exposure and/ or dose)?
How can clonidine be used to decrease dexmedetomidine withdrawal?
C Comparison Can dexmedetomidine be safely weaned in the non-ICU setting?
O Outcome Safe weaning from dexmedetomidine
Decreased ICU length of stay

Mitigation strategies for clinical and operational challenges, including loss of IV access and delay in delivery of medication, were addressed prior to implementation of the guidelines. To prevent errors, dexmedetomidine was supplied to pertinent non-ICU areas only in the standard manufactured concentration of 4 mcg/mL, 100 mL infusion in 0.9% normal saline. Pump libraries were adjusted to include only this concentration in non-ICU areas. The taskforce chair met with interdisciplinary groups from participating units to review the guidelines, eligibility criteria, and safety considerations. If needed due to withdrawal signs and symptoms, clonidine was initiated at 3–5 mcg/kg/d and increased by 2–4 mcg/kg/d daily to a maximum of 25 mcg/kg/d or as patient tolerated. Clonidine rescue for patients with tachycardia and hypertension was dosed at 2.5 mcg/kg/dose and given no more than bid.

Patients were eligible for dexmedetomidine weaning in non-ICU areas if they met the following criteria: Completion of at least two successful consecutive weans while in the ICU with no more than mild-moderate signs of withdrawal; not sedated on the current dose; ready for transfer with regard to other organ systems and therapies; and adequate IV access. Adequate access was defined as either a central venous catheter or a minimum of two peripheral IV lines. In addition, at least 24 hours prior to transfer, eligible patients were referred to the pain consult service to review the patient’s clinical course and to document baseline state.

Patients were identified and followed prospectively. Compliance with the guidelines, days of weaning in non-ICU areas, signs and symptoms of withdrawal, and adverse events were collected prospectively by two nurse practitioners on the pain service. Compliance with the protocol was determined by the same two nurse practitioners by comparing the weaning pattern in the medical record with the guidelines. Because of the large volume of data, vital signs were reviewed but not collected prospectively. The Withdrawal Assessment Tool-1 tool (3), which is routinely used at our institution for weaning various sedatives, does not have sufficient specificity to enumerate some of the signs and symptoms expected when weaning dexmedetomidine. Consequently, we did not use this tool. Instead, we defined moderate withdrawal as sustained tachycardia 10 points greater than baseline and/or sustained hypertension 10–20% greater than baseline and/or agitation and tremors sustained for more than 15 minutes after weaning without other identified causes. Patients with sustained tachycardia and hypertension greater than 20% of the baseline after weaning without other identified causes were considered to have severe withdrawal. To account for age and individual differences in baseline vital signs, we identified baseline vital signs for each patient by graphing the aforementioned vital signs 5 days prior to pain service consultation. A successful wean in non-ICU areas was defined as a completed wean per the guidelines without significant changes in the aforementioned vital signs or observation of withdrawal by the pain team. The number of days the patient weaned dexmedetomidine in non-ICU areas was calculated from the date of transfer from the ICU to non-ICU areas through the date when dexmedetomidine was discontinued.

ICU Pilot

Prior to implementation of guidelines, we performed an ICU pilot involving at least five patients in each of the participating ICUs. The ICU pharmacists identified potential patients according to the above-described criteria. Because the goal of this effort was to trial the guidelines, patients who were not weaned according to the guidelines were excluded from the analysis. Upon review of the results of the ICU pilot, the guidelines were approved by the hospital’s Pharmacy and Therapeutics Committee to wean dexmedetomidine in non-ICU areas.

Implementation in Non-ICU Areas

We identified four non-ICU areas to participate to ensure adequate staff exposure to patients undergoing dexmedetomidine weaning. Prior to implementation to non-ICU areas, the task force created an education plan with written and electronic resources, including a web-based educational module on dexmedetomidine weaning that was completed by 100% of nurses in the participating non-ICU areas. In addition, we conducted in-person educational sessions that included an explanation of the weaning guidelines, assessment of dexmedetomidine withdrawal, contingency plans for safety issues, and resources available to staff. Eligible patients were identified during daily bed management rounds and the pain service was consulted 24 hours before transfer to allow the service to familiarize themselves with the patient and to round with the ICU team prior to transfer. Each patient was billed for the consultation, as per usual practice. Following transfer, the pain service supervised dexmedetomidine weaning according to the guidelines. The pain service is staffed 24/7 with nurse practitioners and an on-call attending physician.

RESULTS

The literature searches were guided by the PICO questions (Table 1). We were unable to identify tools for dexmedetomidine withdrawal. There were no prospective studies of weaning from dexmedetomidine. We identified three retrospective studies of withdrawal symptoms (7,11,12) and the use of clonidine (16–18). One study identified the dose above which withdrawal occurs in critically ill children weaning from dexmedetomidine (7). There was one study describing infants postcardiac surgery who had seizures when weaning (10). Referencing the literature identified and reflecting on clinical practice experience, the taskforce formulated dexmedetomidine weaning guidelines (Fig. 1). Based on the cumulative dose identified by Haenecour et al (7), dexmedetomidine was stopped for patients on dexmedetomidine for less than 5 days and doses of less than 1 mcg/kg/hr. For patients at moderate to high risk of withdrawal based on days and dose of dexmedetomidine or patient’s inability to physiologically tolerate signs and symptoms of withdrawal, dose reductions of dexmedetomidine are outlined in Figure 1. Within the guideline, we provided criteria associated with clinical decompensation in the setting of withdrawal: Those with poor respiratory or cardiac reserves and/or hemodynamic instability, who are unable to tolerate significant increases in heart rate, blood pressure, respiratory rate, or pulmonary vascular resistance. These patients may have single-ventricle physiology, myocardial dysfunction, and/or pulmonary hypertension.

F1
Figure 1.:
Algorithm for weaning dexmedetomidine (dosed in mcg/kg/hr) with interventions for withdrawal based on the patient’s level of risk for withdrawal.

ICU Pilot

The ICU pilot consisted of 21 children for whom the guidelines were followed during 24 episodes of dexmedetomidine weaning. One patient weaned from dexmedetomidine twice after two separate surgeries, while another patient weaned from dexmedetomidine three times during the same admission. Most patients were admitted to the ICU for postsurgical care of conditions including congenital heart disease (n = 5), esophageal atresia (n = 4), tracheobronchomalacia (n = 2), vascular ring (n = 1), and dysplastic tricuspid valve (n = 1). The remainder were admitted for medical management of respiratory failure (n = 7), sepsis (n = 3), and congenital heart disease (n = 1). The median days on dexmedetomidine at time of initial wean was 7.5 days (interquartile range [IQR], 3.5–14.5 d).

The overall dosing range of dexmedetomidine was 0.1–2 mcg/kg/hr. The median maximum dose of dexmedetomidine was 1.5 mcg/kg/hr (IQR, 1.2–2 mcg/kg/hr). Per the guidelines, dexmedetomidine was discontinued without weaning for 10 episodes in which patients were at low risk of withdrawal (exposed to dexmedetomidine for less than 5 d and at dose of < 1 mcg/kg/hr). Only one of these patients had mild signs of withdrawal (irritability), which was managed with comfort measures. Eight patients met the criteria for moderate risk for withdrawal and six were at high risk for withdrawal. There were no adverse events in the pilot related to weaning when using the guidelines.

Implementation in Non-ICU Areas

Upon implementation to non-ICU areas, data were prospectively collected over a 2-year period from October 2018 to September 2020. During this time, 63 patients (1 mo to 18 yr old) met eligibility criteria and all underwent successful weaning of dexmedetomidine in non-ICU areas. All patients were weaned according to the protocol. The majority (n = 35, 56%) were categorized as high risk for withdrawal per weaning criteria. Forty-nine patients (78%) were simultaneously on clonidine when weaning dexmedetomidine. The most frequent weaning interval was 8 hours (n = 40, 62%), and the most frequent weaning decrement was 0.2 mcg/kg/hr (n = 44, 70%). Two patients returned to the ICU without completing the wean: one patient due to respiratory distress related to a pleural effusion and a second patient due to sepsis. Neither of these events was determined to be related to the dexmedetomidine wean, and both of these patients were excluded from the analysis. The median time to discontinuation of dexmedetomidine in non-ICU areas was 5.8 days (IQR, 4.75–15 d).

Most patients experienced mild or no withdrawal (n = 41, 65%). Twenty-two patients (35%) received at least one rescue dose of clonidine for tachycardia and agitation/irritability while weaning dexmedetomidine. Fifteen of these patients also had modifications to the dexmedetomidine weaning schedule via a reduction in the dose decrement and/or increase in the frequency of each wean. Only two patients required an increase in the dexmedetomidine dose back to a prior weaning level.

Adverse events were rare. An urgent IV team consult was called for three patients when IV access was lost. In each of these patients, IVs were placed without symptoms of withdrawal. In addition, one patient with a history of seizures experienced a seizure while weaning dexmedetomidine. The primary team and pain service elected to reduce the rate of weaning from every 8 to every 12 hours. This patient remained in non-ICU areas and no further seizures were noted.

DISCUSSION

We describe an interdisciplinary effort for the development and implementation of guidelines for weaning patients from dexmedetomidine in non-ICU areas. A major facilitator toward this effort was ongoing collaboration between disciplines and units. In addition, throughout this effort, a dedicated team ensured adherence to the guidelines over time. There were no additional personnel costs to the institution to have the pain service manage these patients, as the service was already in place prior to the initiative. Using defined eligibility criteria, all patients safely completed a dexmedetomidine wean in non-ICU areas, and no patient returned to the ICU for reasons related to weaning dexmedetomidine. This effort builds on previous work that describes the beneficial effects of protocolized sedation and weaning guidelines (13,14). In our sample, one patient experienced clinical seizures during dexmedetomidine weaning. There is a article describing infants after cardiovascular surgery who had seizures after an abrupt discontinuation of dexmedetomidine (10). Further evaluation of the association of dexmedetomidine weaning in patients with seizure propensity is warranted. A barrier to implementation of this effort was working with multiple ICUs and units. Education and communication were at times challenging and time consuming.

An unanticipated benefit of this effort was that most patients (75%) returned to a unit where they had been previously admitted. As most of the patients in this study were preverbal and unable to verbally express signs and symptoms of withdrawal, familiarity with the patient’s baseline behaviors may help providers to differentiate baseline behavior from withdrawal while weaning the dexmedetomidine. Further studies describing the signs and symptoms of withdrawal from dexmedetomidine are warranted.

Further research is needed on the optimal use of clonidine to facilitate dexmedetomidine weaning. Clonidine has been shown to mitigate the symptoms of dexmedetomidine withdrawal (16). In animal models, an eight-fold higher affinity of dexmedetomidine to clonidine for alpha 2 receptors was reported (17). However, the direct conversions between the two agents and translation to clinical practice still remain unknown (18,19).

There are several limitations. Vital signs were collected retrospectively from the electronic health record so they may underestimate undocumented withdrawal symptoms. In addition, this effort was implemented in a single institution with 24/7 in-hospital coverage by pain service nurse practitioners with an on-call pain attending and an in-house IV team. These resources may not be available at all institutions. The feasibility of implementing dexmedetomidine weaning in non-ICU areas is contingent upon hospital resources and provider’ training and education. We also note that during the study time period, elective surgeries were canceled due to the COVID-19 pandemic from March 2020 to June 2020, so it is possible that fewer patients were eligible to participate as compared with normal operations.

Weaning dexmedetomidine in non-ICU areas in recently critically ill children is feasible. Standardizing weaning for non-ICU areas may be associated with increased ICU bed utilization and decreased ICU-specific length of stay during hospital admission. The establishment of evidenced-based weaning guidelines, a commitment from all disciplines involved, and a dedicated team were the major contributors to the success of this initiative.

AT THE BEDSIDE

  • Recently, critically ill children can safely wean from dexmedetomidine in non-ICU areas.
  • Weaning dexmedetomidine in non-ICU areas led to shorter ICU stays for patients that met criteria.
  • Written guidelines, a commitment from involved disciplines and a dedicated team were necessary for success.
TABLE 2. - Recommendations for Weaning Dexmedetomidine
Recommendations Evidence
Wean dexmedetomidine based on standardized guidelines. Extrapolated from pediatric opioid and benzodiazepine weaning (13, 14)
Adjust plan for weaning dexmedetomidine based on dose and days of exposure Higher doses and longer exposure to dexmedetomidine prevalence of withdrawal (7)
Wean dexmedetomidine based on the patient’s physiologic ability to tolerate signs and symptoms of withdrawal Extrapolated from opioid and benzodiazepine evidence (13)
Use clonidine to mitigate the signs and symptoms of withdrawal from dexmedetomidine Clonidine has been shown to mitigate the symptoms of dexmedetomidine withdrawal (16). However, there is no direct conversion (16–18)

TABLE 3. - Results of ICU Pilot and Implementation Phase of Patients Weaning From Dexmedetomidine
Category ICU Pilot, n (%) Implementation in Non-ICU Areas, n (%)
n = 24 Episodes n = 63 (%)
Median age, mo (interquartile range) 8 (2–72) 11 (5–25)
Median decrease ICU length of stay Not applicable 5.8 d
Category Total Withdrawal by Level of Risk Total Withdrawal by Level of Risk
Low risk for withdrawal 10 1 (10) 0 0
Moderate risk for withdrawal 8 4 (50) 30 (48) 12 (40)
High risk for withdrawal 6 3 (50) 33 (52) 16 (48)
Weaning interval, hr
 8 16 (67) 38 (60)
 12 8 (33) 18 (29)
 > 12 0 (0) 7 (11)
Withdrawal signs and symptoms (most exhibited more than 1)
 No symptoms 15 (63) 29 (46)
 Tachycardia 4 (17) 25 (40)
 Agitation 5 (21) 9 (14)
 Hypertension 2 (8) 7 (11)
 Tremor 0 (0) 4 (6)
 Sweating 1 (4) 2 (3)
 Dilated pupils 0 (0) 1 (1.5)
 Seizures 0 (0) 1 (1.5)
 Emesis 0 (0) 1 (1.5)

ACKNOWLEDGMENTS

We would like to acknowledge the dedicated providers who participated in this initiative including members of the Pain Service team, inpatient nursing and pharmacy teams, and ICU providers. Also, our thanks goes to Esther Chu and Joel Jerome for their contributions in planning and implementation of this project.

REFERENCES

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Keywords:

clinical practice guidelines; dexmedetomidine; sedative weaning; withdrawal

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