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Dexmedetomidine: A Clinical Review
Seminars in Anesthesia, Perioperative Medicine and Pain (2006) 25, 41-42
Dexmedetomidine: A Clinical Review Dexmedetomidine (Precedex®) is an alpha-2 agonist that was approved in 1999 for sedation in mechanically ventilated patients in the intensive care setting for 24 hours. Although its use in the ICU has been slowly increasing, its use in anesthesia has exploded in recent years. As anesthesia providers continue to become more comfortable and familiar with DMET and more studies are conducted, its use will assuredly continue to increase. DMET is a highly selective alpha-2 adrenoreceptor agonist which has analgesic and sedative effects with little effect on ventilation. In addition, it has been proposed to be both cardioprotective and neuroprotective. This pharmacologic profile, combined with a very impressive safety margin, has made it an attractive choice for anesthesiologists and intensivists. Prospective, randomized, placebo-controlled studies using DMET are still limited and much of the available information comes from case reports and case series. In addition, at approximately $50 for a 200 mcg vial, the cost of DMET is not insignificant. However, the information available is extremely promising, and the cost can likely be justified by the apparent clinical benefits. In this issue, we offer a review of some of the clinical uses of DMET. While some recent areas of interest for uses of DMET have not been included, this compendium represents a relatively complete review of the DMET clinical literature and includes some areas of theoretical interest.
Pandharpipande, Ely, and Maze: Dexmedetomidine for sedation and perioperative management of critically ill patients Sedation in mechanically ventilated intensive care patients for the first 24 hours is currently the only FDA approved indication for DMET. Its sedative and analgesic characteristics without respiratory depression make DMET ideal in the intensive care setting. Limited data on the safety of prolonged infusions of DMET has somewhat limited its use, however. Despite its superior pharmacologic profile when compared with more classical benzodiazepine and opioid combinations, cost could be prohibitive. The authors have created an excellent review of the pharmacologic principles key to the use of DMET in critically ill patients in the perioperative period and intensive 0277-0326/$ -see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1053/j.sane.2006.03.001
care setting. They offer some perspective on reasons for considering DMET over more traditional methods of sedation and pain management.
Ramsay: Bariatric surgery: The role of dexmedetomidine Obesity is a growing problem in the United States and throughout the rest of the world. Obesity affects every organ system and is a major source of morbidity and mortality. Recent studies have indicated long term benefits from bariatric surgery associated with the reduction in diabetes mellitus, hypertension, and gastroesophageal reflux disease. Because of the apparent benefits, the number of bariatric surgeries is increasing each year. Yet, the anesthetic risk remains high. Dr. Ramsay provides an excellent review of the basics of bariatric surgery and its anesthetic and surgical risks. He discusses the benefits DMET can offer by providing cardiovascular stability, cardioprotection, opioid-sparing analgesia, sedation, and airway protection. He also kindly offers a cookbook-style clinical application modeled on his vast clinical experience.
Tobias: Clinical uses of dexmedetomidine in pediatric anesthesiology and critical care Although not approved in children, the use of DMET in pediatric anesthesia and intensive care is increasing. The beneficial drug profile extends to pediatrics. Much of the pediatric literature is in the form of case reports and case series. There are some studies, however, comparing DMET to more conventional methods of sedation. Dr. Tobias discusses sedation for mechanical ventilation, intraoperative applications, procedural sedation, prevention of postoperative delirium and agitation, and treatment of withdrawal.
Unger and Gallagher: Dexmedetomidine sedation for awake fiberoptic intubation Awake fiberoptic intubations can be uncomfortable for both the anesthesiologist and the patient. Although important for the success of the intubation and comfort of the patient, sedation can be extremely tricky. The “cooperative seda-
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Seminars in Anesthesia, Perioperative Medicine and Pain, Vol 25, No 2, June 2006
tion” afforded by DMET can make airway preparation and fiberoptic intubation easier, without compromising the patient’s respiratory drive. In addition, the cardiovascular effects of DMET can ease the sympathetic storm that often comes with airway manipulation during intubation and extubation. Dr. Unger and Dr. Gallagher have written a great review of the use of DMET in difficult airways, and they compare DMET to more traditional methods of sedation. The authors are also kind enough to share their vast clinical experience by offering some clinical tips.
Janke and Samra: Dexmedetomidine and neuroprotection Neuroprotection has been a subject of much debate for some time. A multitude of measures have been employed with varied success. Clinical trials evaluating neuroprotective measures would be extremely difficult to design and would require huge numbers of patients. Therefore, we must look to retrospective and laboratory studies to gain insight. Dr. Janke and Dr. Samra begin with an explanation of the ideal characteristics of a neuroprotectant and the basics of the pathogenesis of cell death. They then discuss the evidence favoring alpha-2 agonists as neuroprotectants. Though much of the available literature comes from the laboratory, the role of DMET in neuroprotection is intriguing and warrants further investigation.
Wagner and Brummett: Dexmedetomidine: As safe as safe can be Evaluation of the safety of new drugs is critical. After several years of clinical experience in intensive care and anesthesia, DMET appears to have a large safety margin.
Synergy with benzodiazepines is one area of particular concern for anesthesiologists. This article offers an overall systematic approach to the pharmacologic effects of DMET. Overdosing and side-effects are also discussed. Prolonged infusions in the intensive care setting appear to be safe. Until more studies evaluating prolonged infusions are conducted, however, it is difficult to draw any firm conclusions.
Brummett and Wagner: The use of alpha-2 agonists in peripheral nerve blocks: A review of the history of clonidine and a look at a possible future for dexmedetomidine Regional anesthesia is a growing field, and anesthesiologists are constantly searching for new methods to keep patients comfortable longer. Many additives to local anesthetics have been studied. Clonidine, another alpha-2 agonist, has been used for years as an additive to local anesthetics to prolong the duration of peripheral nerve blocks. The mechanism for improved blockade and the efficacy with long acting local anesthetics have been somewhat controversial topics. In this article, the authors review the clinical literature using clonidine in peripheral nerve blocks and the laboratory studies investigating the mechanism. The limited literature using DMET in regional anesthesia is then reviewed and a possible future for DMET in peripheral nerve blocks is proposed. I would like to thank Dr. Philip Lumb and Dr. Ralph Lydic for this wonderful opportunity. In addition, thank you to all of the authors. I am honored to have worked with such a distinguished group. Chad M. Brummett, MD Guest Editor
Dexmedetomidine: A Clinical Review Dexmedetomidine (Precedex®) is an alpha-2 agonist that was approved in 1999 for sedation in mechanically ventilated patients in the intensive care setting for 24 hours. Although its use in the ICU has been slowly increasing, its use in anesthesia has exploded in recent years. As anesthesia providers continue to become more comfortable and familiar with DMET and more studies are conducted, its use will assuredly continue to increase. DMET is a highly selective alpha-2 adrenoreceptor agonist which has analgesic and sedative effects with little effect on ventilation. In addition, it has been proposed to be both cardioprotective and neuroprotective. This pharmacologic profile, combined with a very impressive safety margin, has made it an attractive choice for anesthesiologists and intensivists. Prospective, randomized, placebo-controlled studies using DMET are still limited and much of the available information comes from case reports and case series. In addition, at approximately $50 for a 200 mcg vial, the cost of DMET is not insignificant. However, the information available is extremely promising, and the cost can likely be justified by the apparent clinical benefits. In this issue, we offer a review of some of the clinical uses of DMET. While some recent areas of interest for uses of DMET have not been included, this compendium represents a relatively complete review of the DMET clinical literature and includes some areas of theoretical interest.
Pandharpipande, Ely, and Maze: Dexmedetomidine for sedation and perioperative management of critically ill patients Sedation in mechanically ventilated intensive care patients for the first 24 hours is currently the only FDA approved indication for DMET. Its sedative and analgesic characteristics without respiratory depression make DMET ideal in the intensive care setting. Limited data on the safety of prolonged infusions of DMET has somewhat limited its use, however. Despite its superior pharmacologic profile when compared with more classical benzodiazepine and opioid combinations, cost could be prohibitive. The authors have created an excellent review of the pharmacologic principles key to the use of DMET in critically ill patients in the perioperative period and intensive 0277-0326/$ -see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1053/j.sane.2006.03.001
care setting. They offer some perspective on reasons for considering DMET over more traditional methods of sedation and pain management.
Ramsay: Bariatric surgery: The role of dexmedetomidine Obesity is a growing problem in the United States and throughout the rest of the world. Obesity affects every organ system and is a major source of morbidity and mortality. Recent studies have indicated long term benefits from bariatric surgery associated with the reduction in diabetes mellitus, hypertension, and gastroesophageal reflux disease. Because of the apparent benefits, the number of bariatric surgeries is increasing each year. Yet, the anesthetic risk remains high. Dr. Ramsay provides an excellent review of the basics of bariatric surgery and its anesthetic and surgical risks. He discusses the benefits DMET can offer by providing cardiovascular stability, cardioprotection, opioid-sparing analgesia, sedation, and airway protection. He also kindly offers a cookbook-style clinical application modeled on his vast clinical experience.
Tobias: Clinical uses of dexmedetomidine in pediatric anesthesiology and critical care Although not approved in children, the use of DMET in pediatric anesthesia and intensive care is increasing. The beneficial drug profile extends to pediatrics. Much of the pediatric literature is in the form of case reports and case series. There are some studies, however, comparing DMET to more conventional methods of sedation. Dr. Tobias discusses sedation for mechanical ventilation, intraoperative applications, procedural sedation, prevention of postoperative delirium and agitation, and treatment of withdrawal.
Unger and Gallagher: Dexmedetomidine sedation for awake fiberoptic intubation Awake fiberoptic intubations can be uncomfortable for both the anesthesiologist and the patient. Although important for the success of the intubation and comfort of the patient, sedation can be extremely tricky. The “cooperative seda-
42
Seminars in Anesthesia, Perioperative Medicine and Pain, Vol 25, No 2, June 2006
tion” afforded by DMET can make airway preparation and fiberoptic intubation easier, without compromising the patient’s respiratory drive. In addition, the cardiovascular effects of DMET can ease the sympathetic storm that often comes with airway manipulation during intubation and extubation. Dr. Unger and Dr. Gallagher have written a great review of the use of DMET in difficult airways, and they compare DMET to more traditional methods of sedation. The authors are also kind enough to share their vast clinical experience by offering some clinical tips.
Janke and Samra: Dexmedetomidine and neuroprotection Neuroprotection has been a subject of much debate for some time. A multitude of measures have been employed with varied success. Clinical trials evaluating neuroprotective measures would be extremely difficult to design and would require huge numbers of patients. Therefore, we must look to retrospective and laboratory studies to gain insight. Dr. Janke and Dr. Samra begin with an explanation of the ideal characteristics of a neuroprotectant and the basics of the pathogenesis of cell death. They then discuss the evidence favoring alpha-2 agonists as neuroprotectants. Though much of the available literature comes from the laboratory, the role of DMET in neuroprotection is intriguing and warrants further investigation.
Wagner and Brummett: Dexmedetomidine: As safe as safe can be Evaluation of the safety of new drugs is critical. After several years of clinical experience in intensive care and anesthesia, DMET appears to have a large safety margin.
Synergy with benzodiazepines is one area of particular concern for anesthesiologists. This article offers an overall systematic approach to the pharmacologic effects of DMET. Overdosing and side-effects are also discussed. Prolonged infusions in the intensive care setting appear to be safe. Until more studies evaluating prolonged infusions are conducted, however, it is difficult to draw any firm conclusions.
Brummett and Wagner: The use of alpha-2 agonists in peripheral nerve blocks: A review of the history of clonidine and a look at a possible future for dexmedetomidine Regional anesthesia is a growing field, and anesthesiologists are constantly searching for new methods to keep patients comfortable longer. Many additives to local anesthetics have been studied. Clonidine, another alpha-2 agonist, has been used for years as an additive to local anesthetics to prolong the duration of peripheral nerve blocks. The mechanism for improved blockade and the efficacy with long acting local anesthetics have been somewhat controversial topics. In this article, the authors review the clinical literature using clonidine in peripheral nerve blocks and the laboratory studies investigating the mechanism. The limited literature using DMET in regional anesthesia is then reviewed and a possible future for DMET in peripheral nerve blocks is proposed. I would like to thank Dr. Philip Lumb and Dr. Ralph Lydic for this wonderful opportunity. In addition, thank you to all of the authors. I am honored to have worked with such a distinguished group. Chad M. Brummett, MD Guest Editor