How does precedex cause bradycardia

Dexmedetomidine exposure is mainly governed by its hepatic clearance. Hepatic impairment was shown to have an impact on the pharmacokinetics and should therefore be taken into account when choosing a dosing regimen.

From the reported PK studies, it seems that the bodyweight-adjusted dosing that is currently applied is only justified for non-obese patients. For obese patients, other body size descriptors, e. Evidence in favour of the influence of other patient characteristics, such as plasma albumin levels, cardiac output, and age is less convincing. The sedative, analgesic, and cardiovascular effects of dexmedetomidine are well described.

Respiratory depression is unlikely when dexmedetomidine is used alone. However, recent reports suggest that when it is combined with other sedatives or hypnotics, there is an increased risk, necessitating continuous respiratory monitoring. Other PD interactions as well as PK interactions have been described. Some of these, e. Effects of intravenous dexmedetomidine in humans. Sedation, ventilation, and metabolic rate. US Food and Drug Administration. Precedex label. Accessed 14 Nov European Medicines Agency.

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Three intubated patients receiving fentanyl and dexmedetomidine infusion developed sudden bradycardia requiring intervention. In all three cases, adjustments to therapy were required. In all three cases, there were no further incidences of significant bradycardia following intervention. Fentanyl used in combination with dexmedetomidine can result in clinically significant bradycardia.

Further study is warranted to identify risk factors and elucidate the mechanisms that result in life-threatening bradycardia. The current pain, agitation, and delirium guidelines encourage the use of fentanyl with sedation strategies using nonbenzodiazepine sedatives [ 1 ]. Dexmedetomidine is an effective sedative that is often used in conjunction with opioids such as fentanyl in the critical care and anesthesia setting. Bradycardia and hypotension are well-known associations with dexmedetomidine, yet no human studies have examined the occurrence of drug-induced bradycardia secondary to the combination of dexmedetomidine and fentanyl.

One study demonstrated attenuation of the tachycardia response to flexible bronchoscopy with the combination of dexmedetomidine-fentanyl compared to propofol-fentanyl [ 2 ]. Here we report three cases in which a synergistic interaction between fentanyl and dexmedetomidine may have contributed to clinically relevant bradycardia.

Patient was a year-old male with a past medical history of cirrhosis, ulcerative colitis, esophageal varices with previous banding, hypertension, and hyperlipidemia. He had advanced alcoholic cirrhosis, with a Model for End-Stage Liver Disease MELD score of 17, and was admitted with a large right pleural effusion secondary to ascites.

His initial pharmacologic management included furosemide, spironolactone, albumin, midodrine, pantoprazole, lactulose, rifaximin, and antibiotics for a possible pneumonia. Despite multiple thoracenteses, he ultimately required intubation on hospital day six secondary to worsening respiratory failure. His weight and select values at this time are provided in Table 1. He was initially sedated with propofol alone, which was changed to dexmedetomidine after a few hours due to persistent agitation.

Approximately 30 hours later, while receiving dexmedetomidine 0. As both infusion rates were decreased, the heart rate steadily improved further. Ultimately, the patient was maintained on dexmedetomidine 0.

His blood pressure remained stable throughout the entire duration of mechanical ventilation. The patient remained intubated until hospital day 11, when he again became agitated, requiring dexmedetomidine to be increased from 0. The patient had no other medications or precipitating factors that would be expected to contribute to bradycardia. Patient was a year-old male with a history of metastatic breast cancer, cholangiocarcinoma, atrial fibrillation, and hyperthyroidism who was initially admitted to the hospital with abdominal pain and found to have a yeast infection in his peritoneal fluid.

After seven days in the hospital, he was transferred to the ICU for septic shock due to E. Despite vasopressor therapy, the patient remained in a persistent shock state and subsequently developed multiorgan failure. Upon ICU admission, the patient was intubated for respiratory failure and initially received propofol and fentanyl for sedation and analgesia but was switched to dexmedetomidine alone due to hypotension.

Throughout his ICU course, he required continuous renal replacement therapy and total parenteral nutrition. Dexmedetomidine was titrated up to 0. Dexmedetomidine infusion was immediately discontinued, and the heart rate ultimately improved to normal without intervention. The patient was switched to midazolam infusion, and there were no further episodes.

During the time of the asystole, the patient was also receiving rifaximin for a resolving hyperammonemia, famotidine, heparin, cefazolin, insulin, methimazole, metoclopramide, and norepinephrine.

Select labs at this time are provided in Table 1. The patient ultimately expired on hospital day 21 due to cardiac arrest following a prolonged course.

A year-old male admitted with myasthenia gravis, benign prostate hypertrophy, and hyperlipidemia was admitted with myasthenia gravis crisis. He was initially treated with intravenous immunoglobulin but required intubation on day 2 for airway management and was later treated with plasmapheresis. During his intubation, he was initially sedated with continuous infusions of fentanyl and propofol. On day 4 of his hospital course, he was switched from propofol and fentanyl to dexmedetomidine monotherapy at doses between 0.

On day 9, dexmedetomidine was again added to his sedation regimen to facilitate extubation and titrated slowly to 0.

In response to the heart rate, fentanyl was discontinued, followed by dexmedetomidine, and finally propofol, all within two hours of each other. The heart rate began to increase back to normal within 30 minutes of discontinuing all three infusions. No other sedative agent was added after this, and the patient was successfully extubated the next day with no further hemodynamic complications and was discharged to a rehabilitation center after a prolonged hospital course.

During the bradycardia episode, the patient was receiving methylprednisolone, quetiapine started four days earlier for agitation , heparin, famotidine, and ceftriaxone and was on his fifth day of plasmapheresis therapy. He did not receive pyridostigmine until the last day of his hospitalization and had no other precipitating factors for bradycardia. Based on a model of simulated concentration, a concentration of 0. Depression of cardiac function would have been induced when the plasma concentration of dexmedetomidine exceeded 1.

Takada et al. There is no data in the literature regarding the coadministration of dexmedetomidine with many other drugs.

However, the combination of dexmedetomidine with benzodiazepines has been used for the treatment of alcohol withdrawal syndrome.

Double blind randomized trials demonstrated a statistically better outcome in the group receiving dexmedetomidine and benzodiazepines compared to the benzodiazepine monotherapy group. Nevertheless, bradycardia was reported as a common event with dexmedetomidine [ 6 ]. Another key point is the possible interaction between dexmedetomidine and pregabalin. While there are no reports regarding their coadministration, pregabalin has been found to lower heart rate and attenuate sympathetic outflow during laryngoscopy [ 7 ].

The introduction of dexmedetomidine offers the anesthetist many advantages without causing respiratory depression. But it does not lack other side effects with bradycardia being the prominent one. For this reason, it is mandatory to have a standard monitoring as well as the alertness to manage critical incidents. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors. Read the winning articles. Journal overview. A Corrigendum for this article has been published. Academic Editor: Neerja Bhardwaj. Received 17 Aug Revised 08 Nov Accepted 25 Nov Published 05 Dec Abstract Dexmedetomidine is an elective alpha-2 adrenergic agonist, being used in anesthesia practice.

Introduction Dexmedetomidine is unique for its sedative and anxiolytic properties in the operating room or intensive care unit, due to its minimal respiratory effects [ 1 ]. Discussion Bradycardia and asystole after dexmedetomidine infusion is a well-described phenomenon [ 4 ]. Conflicts of Interest The authors declare that they have no conflicts of interest.

References G.