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Dexmedetomidine as a Rescue Therapy for Emergence Delirium in Adults: A Case Series

Read, Matthew D. MD; Maani, Christopher V. MD; Blackwell, Scott MD

doi: 10.1213/XAA.0000000000000510
Case Reports: Case Report
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Emergence delirium (ED) in adult patients encountered in the postanesthesia care unit (PACU) is not well studied; nor are ED treatment strategies. Similar to delirium in the intensive care unit, ED in the PACU can result in serious complications. We describe 3 cases of ED in the PACU in patients with a history of posttraumatic stress disorder who were successfully treated with dexmedetomidine. Although likely utilized more frequently in recent years, the use of dexmedetomidine in the PACU for treatment of ED is not established in the literature. Further research regarding treatment of ED in adults is necessary, allowing for optimization of patient care and improvement in patient outcomes.

From the Department of Anesthesiology, San Antonio Military Medical Center, Joint Base San Antonio Fort Sam Houston, Texas.

Accepted for publication January 6, 2017.

Funding: None.

The authors declare no conflicts of interest.

Address correspondence to Matthew D. Read, MD, Department of Anesthesiology, San Antonio Uniformed Services Health Education Consortium, Joint Base San Antonio Fort Sam Houston, 9207 Blazing Star Trail, Garden Ridge, TX 78266. Address e-mail to mdreadmd@gmail.com.

Emergence delirium (ED) is an acute change in cognition characterized by fluctuating consciousness and attention that occurs in the immediate recovery period after anesthesia.1 The incidence of ED, prevention, and treatment strategies in the pediatric population are well known and described in the literature. However, in adults, these are not well established. Only 2 studies have shown an incidence of ED in adults of 3.7% to 4.7%.1,2 Just as in the intensive care unit (ICU), patients in the postanesthesia care unit (PACU) with ED often require longer postoperative recovery periods, utilize significantly more resources, and demonstrate greater risk for harm to themselves or their health care providers.2

Alternative diagnoses for, and causes of, ED are broad and include numerous physiologic etiologies, many of which may be immediately reversed.3,4 In addition, pharmacologic agents, many of which are administered in the perioperative time period, and timing of administration, may also cause ED.3,4Table 1 lists alternative diagnoses and potential pharmacologic causes of ED. The potential of several of these agents to be both therapeutic and exacerbative makes clinical decision making even more challenging when it comes to the timely management of patients with ED. In the absence of a reversible physiologic cause of ED, or while awaiting correction of the cause, pharmacologic therapy is indicated. In the 3 cases described here, we demonstrate the judicious and successful use of dexmedetomidine for rescue of ED in adults. Written consent was obtained from all patients for presentation and publication of this case series.

Table 1.

Table 1.

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Consent for Publication

The primary author, Matthew D. Read, MD, had direct participation in the care provided to the patients in the presented cases. All patients have been deidentified, and no collection of personally identifiable information was collected.

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CASE DESCRIPTION

Case 1

A 33-year-old, 80-kg, American Society of Anesthesiologists (ASA) physical status (PS) II male with cervical radiculopathy underwent a 2-level anterior cervical discectomy and fusion. His medical history was significant for obstructive sleep apnea. He had undergone 2 previous general anesthetics without any noted complications. His medications included gabapentin, amitriptyline, and celecoxib. He had previous adverse reactions to hydrocodone/acetaminophen combination resulting in mild nausea and vomiting; however, he had no true medication allergies. His social history was negative for tobacco or illicit substances, but he did endorse alcohol consumption on a rare basis.

On the morning of surgery, the patient was premedicated with midazolam for anxiolysis and glycopyrrolate in preparation for an asleep fiberoptic intubation. Induction of general anesthesia was accomplished with lidocaine, propofol, sufentanil, and succinylcholine, followed by successful oral fiberoptic intubation with an endotracheal tube (ETT). Maintenance of anesthesia was accomplished with a total intravenous (IV) anesthetic consisting of propofol and remifentanil infusions for the duration of this 4-hour procedure. He was also given ketamine and dexamethasone before incision. Before emergence, hydromorphone, acetaminophen, and ondansetron were administered. After confirming the absence of residual paralysis, no pharmacologic reversal of neuromuscular blockade was deemed necessary. The patient was successfully extubated in the operating room (OR) and transported to the PACU.

On arrival to the PACU, the patient began to voice recall of his previous military combat experiences. Although not combative, he was agitated, tachycardic, and hypertensive. There was no evidence of any reversible causes of delirium. His Richmond Agitation and Sedation Scale (RASS) score was +2. Attempts were made to verbally reorient the patient unsuccessfully. Pharmacologic interventions including midazolam and physostigmine were also unsuccessful. Of note, upon bringing the patient’s wife into the PACU in an attempt to aid in reorientation, we were advised of his history of posttraumatic stress disorder (PTSD). An IV bolus of 0.5 mcg/kg of dexmedetomidine was administered. An IV infusion of dexmedetomidine was then started at 0.5 mcg/kg/h, which was titrated off over the ensuing hour. Immediately after the initial bolus of dexmedetomidine, the patient became hemodynamically normal and no longer demonstrated any delirium, soon conversing appropriately, with a RASS score of 0. He was monitored in the PACU per standard protocol, and after discharge criteria were met, he was transferred to the ward. On postoperative evaluation, the patient denied any recall of the events in the PACU and had no additional episodes of delirium.

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Case 2

A 40-year-old, 101-kg, ASA PS II female underwent open reduction and internal fixation of her right ankle 1 day after a fall from a second-story balcony. Her medical history was significant for obesity, PTSD, and paranoid schizophrenia. She had undergone 2 previous general anesthetics without any noted complications. Her medications included quetiapine, amitriptyline, and lorazepam. She did not have any medication allergies. Her social history was positive for the use of crack cocaine, tobacco, and alcohol.

Before transport to the OR, the patient was premedicated with midazolam for anxiolysis. Induction of general anesthesia was accomplished with lidocaine, propofol, hydromorphone, and succinylcholine, followed by successful placement of an oral ETT. For the next 4 hours, maintenance of anesthesia was accomplished with sevoflurane, hydromorphone, and rocuronium. Before emergence, acetaminophen and ondansetron were administered. After confirming the absence of residual paralysis, no pharmacologic reversal of neuromuscular blockade was deemed necessary. She was successfully extubated in the OR and transported to the PACU.

On emergence in the PACU, the patient became agitated and combative, complaining of a pain rating of “2 million” out of 10. In her postoperative delirium, she was neither alert nor oriented, with a RASS score of +4. After a brief physical exam, there was no clear etiology or evidence of any reversible causes of delirium. Intermittent doses of fentanyl and hydromorphone were administered without success in treatment of her pain; further, she was becoming more agitated and combative. A bolus of 1 mcg/kg of dexmedetomidine was administered via IV. An IV infusion of dexmedetomidine was started at 0.5 mcg/kg/h, which was titrated off over the course of 2 hours. The patient was transferred to the ward without agitation or combativeness, although with intermittent delusional behavior and a RASS score of +1. A behavioral consult was placed by the surgical team for continued management while she was an inpatient. Of note, the patient reported heavy use of oxycodone and methadone as an outpatient, although this was absent from her medical record and not administered throughout her preoperative hospital course. She was later discharged without further adverse events.

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Case 3

A 49-year-old, 86-kg, ASA PS II male with chronic lumbago and left lower extremity radiculopathy underwent a single-level posterior lumbar interbody fusion. His medical history was significant for obstructive sleep apnea, insomnia, migraines, benign prostatic hypertrophy, and PTSD. The patient had undergone 6 previous general anesthetics without any noted complications. His only outpatient medication was escitalopram. He did not have any medication allergies. His social history was negative for tobacco, alcohol, and illicit substances.

The patient was premedicated with midazolam for anxiolysis. Induction of general anesthesia was accomplished with lidocaine, propofol, fentanyl, and rocuronium, followed by successful placement of an oral ETT. Maintenance of anesthesia was accomplished with sevoflurane, fentanyl, and hydromorphone for the duration of the 2-hour procedure. He was also administered acetaminophen and dexamethasone for postoperative nausea and vomiting prophylaxis. Before emergence, ketorolac and ondansetron were administered. After confirming the absence of residual paralysis, no pharmacologic reversal of neuromuscular blockade was deemed necessary. On emergence, the patient was extremely combative. Because it was thought that his combativeness was secondary to remaining intubated with a “light plane of anesthesia,” he was successfully extubated in the OR.

Before leaving the OR, the patient was breathing spontaneously but remained combative, with a RASS score of +4. He was administered IV boluses of midazolam and fentanyl. On arrival to the PACU, the patient’s status had not changed. There was no evidence of any reversible causes of delirium. An IV bolus of valium was administered, again without significant improvement in the patient’s condition. Then, an IV bolus of 1 mcg/kg of dexmedetomidine was administered. An IV infusion of dexmedetomidine was started at 0.7 mcg/kg/h and eventually increased to 1 mcg/kg/h. The patient remained in the PACU, with a RASS score of 0, on the dexmedetomidine infusion, which was eventually titrated off after 2 hours. Afterward, with the patient noted to be noncombative and cooperative, discharge criteria were met, and the no further sequelae were noted. The patient recovered uneventfully and was discharged home.

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DISCUSSION

These 3 cases describe the successful treatment of ED using dexmedetomidine after general anesthesia in adults. There was an array of preoperative comorbidities and chronic medication usage, in addition to techniques utilized for induction and maintenance of general anesthesia, many of which are risk factors for the development of ED. All 3 cases occurred in patients with a history of PTSD, an independent predictor of developing ED, especially with agitation.5 All 3 patients received premedication with midazolam. Maintenance of anesthesia was achieved with a volatile anesthetic for 2 of the procedures and with total intravenous anesthetic for 1. All 3 patients received perioperative opioids, 1 patient received ketamine, and 2 of the 3 patients received dexamethasone for postoperative nausea and vomiting prophylaxis. Therapies other than dexmedetomidine to treat pain and agitation were attempted for all 3 patients before administration of dexmedetomidine, including reorientation and, in one instance, bringing a patient’s spouse to bedside.

RASS and Aldrete scores improved in all 3 cases after initiation of therapy with dexmedetomidine (Table 2), allowing appropriate disposition from the PACU. The RASS score (Table 3) is a validated instrument for assessing agitation and sedation in critically ill patients, allowing goal-directed administration of sedation and analgesia.6 Although likely utilized more frequently to wean sedation in the ICU, the RASS as an assessment tool of agitation in the PACU may aid in appropriate goal-directed management of patients with ED. In all 3 cases, the patients were calmer after administration of dexmedetomidine. The Aldrete scores on arrival to PACU were low, affected by all components of the Aldrete score (Table 4), perhaps because of ED. Alterations in Aldrete score for these patients while experiencing ED were most notable in level of consciousness, hemodynamics, and oxygenation.

Table 2.

Table 2.

Table 3.

Table 3.

Table 4.

Table 4.

Dexmedetomidine was administered as an IV bolus (range, 0.5–1 mcg/kg) with IV infusions being initiated (range, 0.5–0.7 mcg/kg/h) in all 3 cases. Dexmedetomidine has a favorable pharmacokinetic and pharmacodynamic profile for use perioperatively for the treatment of ED. The sedation produced by dexmedetomidine is unique in that patients are easily arousable with minimal respiratory depression,7 thus, infusions may be continued in patients amidst emergence from anesthesia. Dexmedetomidine has a rapid distribution, short half-life, and metabolism is minimally impacted by age or comorbidities.8

The use of intraoperative dexmedetomidine has been shown to decrease the frequency and severity of ED in children, with single doses ranging from 0.15 to 1 mcg/kg.9 Intraoperative administration of dexmedetomidine has also been shown to decrease the incidence of delirium in adults after cardiac surgery10 and otolaryngology procedures.11 Delirium from various nonoperative causes has also been successfully treated with dexmedetomidine, including substance abuse and withdrawal and traumatic brain injury.12 Furthermore, the utilization of dexmedetomidine for prevention and treatment of postoperative delirium in the ICU has been shown in multiple comparative studies, systematic reviews, and meta-analyses.13–15 However, to our knowledge, no reports of dexmedetomidine for use as a rescue modality for ED have been described, in both the adult and pediatric literature. Because the PACU is a natural extension of the ICU, it could be presumed that dexmedetomidine is advantageous in the PACU for the treatment of ED, and we have demonstrated this in the presented cases.

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CONCLUSIONS

ED in adult patients encountered in the PACU is not well studied, nor are ED treatment strategies. It is likely encountered in this population more frequently than recognized. Many perioperative factors can lead to ED, especially including the presence of PTSD and pharmacologic agents administered. ED in adults is dangerous and can have serious consequences to both the patient and treating providers. Dexmedetomidine has a favorable pharmacokinetic and pharmacodynamics profile especially suited for this situation. More research is required to further delineate best practices to promote safe and optimal care of this patient population. With this case series, we highlight the potential utility and efficacy of dexmedetomidine as rescue therapy for adult patients with ED in the PACU, thus maximizing clinical outcomes and patient safety.

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DISCLAIMER

The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Brooke Army Medical Center, the US Army Medical Department, the US Army Office of the Surgeon General, the Department of the Army, the Department of the Air Force, Department of Defense, or the US Government.

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DISCLOSURES

Name: Matthew D. Read, MD.

Contribution: This author helped care for the patients, and develop and edit the manuscript.

Name: Christopher V. Maani, MD.

Contribution: This author helped care for the patients, critically assess the manuscript, and edit the manuscript.

Name: Scott Blackwell, MD.

Contribution: This author helped care for the patients, critically assess the manuscript, and edit the manuscript.

This manuscript was handled by: Raymond C. Roy, MD.

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