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Anesth Analg 2003;96:1054-1055 © 2003 International Anesthesia Research Society
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Abstract |
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 Top Abstract IntroductionCase ReportDiscussionReferences |
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IMPLICATIONS: Dexmedetomidine, an 
2-adrenoceptor agonist, is indicated for sedating patients on mechanical ventilation. It has been approved by the Food and Drug Administration for 24-h use. This is a report concerning a patient in whom a continuous infusion of dexmedetomidine was safely used for a week to help in averting frank withdrawal symptoms from an opioid and benzodiazepines.
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Introduction |
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TopAbstractIntroductionCase ReportDiscussionReferences |
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The patient was a multiple-substance abuser admitted to the intensive care unit (ICU) with acute respiratory distress syndrome (ARDS), subsequently complicated by ventilator-associated pneumonia (VAP). He required long-term sedation with multiple drugs with potential addiction and withdrawal complications. We started dexmedetomidine IV after we were unable to wean him from mechanical ventilation. Over 7 days on dexmedetomidine, he was successfully weaned from the ventilator, lorazepam, and IV fentanyl without withdrawal symptoms, adverse events, or sequelae.
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Case Report |
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TopAbstractIntroductionCase ReportDiscussionReferences |
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A 33-yr-old man with a history of substance abuse with cocaine, ketamine, marijuana, and benzodiazepines presented to the emergency department with recent-onset shortness of breath and pleuritic chest pain. Before arrival, he had used an unknown quantity of intranasal ketamine. He was febrile (38.3°C), was hypotensive with a blood pressure of 77/52 mm Hg, and had a heart rate of 146 bpm, a respiratory rate of 22 breaths/min, and an oxygen saturation of 87% on 100% oxygen. Lung examination revealed coarse bilateral breath sounds with crackles. Cardiac examination revealed tachycardia that was regular with no murmurs, rubs, or gallops. The rest of his physical examination was unremarkable.
The patient was very agitated and had to be sedated and restrained. A chest radiograph showed bilateral alveolar infiltrates encompassing the entire field in both lungs. An endotracheal tube was introduced, and he was sedated with propofol (30 µg · kg-1 · min-1) and lorazepam (2 mg/h).
He remained persistently hypotensive and was started empirically on broad-spectrum antibiotics for possible septic shock. An echocardiogram showed global ventricular dysfunction. A right heart catheter subsequently revealed a pulmonary capillary wedge pressure of 24 mm Hg with a cardiac output of 2.1 L/min. Inotropic therapy significantly improved his hemodynamic profile.
A repeat echocardiogram showed normalization of biventricular function. There was no improvement in his chest radiograph or oxygenation status, and his clinical picture was consistent with ARDS. He maintained an oxygen saturation of 89% on 100% oxygen with positive end-expiratory pressure (PEEP) to 15 cm H2O. He was then paralyzed with cisatracurium. Lorazepam and propofol were continued, and fentanyl (100 µg/h) was added.
His ICU course was complicated by an episode of VAP with Acinetobacter baumannii. Mechanical ventilation could not be discontinued because of persistently large oxygen requirements. On Day 17, a tracheostomy was performed. On Day 18, methylprednisolone was started at 2 mg/kg.
His oxygenation status slowly improved, and by Day 21 he was maintained on 40% oxygen with a PEEP of 5 cm H2O. Cisatracurium was discontinued, but he remained tachycardic and febrile. At this point, he was still being maintained on lorazepam, propofol, and fentanyl. In an attempt to taper the lorazepam and fentanyl, haloperidol was added at 20 mg every 4 h. Despite propofol doses in the range of 50 µg · kg-1 · min-1 and a fentanyl patch (25 µg), attempts at weaning from lorazepam or fentanyl resulted in persistent fevers, tachycardia, and tachypnea.
On Day 25, an IV infusion of dexmedetomidine was started at 0.7 µg · kg-1 · h-1 without a bolus dose. This medication was chosen with the hope that the 2-adrenoceptor agonist effects would help with symptoms related to withdrawal from opioids and benzodiazepines. With the combination of dexmedetomidine and the fentanyl patch, we discontinued the lorazepam and IV fentanyl. On Day 28 (Day 3 of dexmedetomidine), we began to taper haloperidol. On Day 4, dexmedetomidine was decreased to 0.5 µg · kg-1 · h-1. The patient awoke and was alert, oriented, and cooperative. While still receiving dexmedetomidine, he was successfully weaned form the ventilator. On Day 6, dexmedetomidine was decreased to 0.2 µg · kg-1 · h-1; on Day 7, it was stopped. No hemodynamic sequelae were observed during the entire time of dexmedetomidine infusion. The patient was eventually weaned from the fentanyl patch, angiocatheters were removed, and he was transferred to a rehabilitation facility.
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Discussion |
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TopAbstractIntroductionCase ReportDiscussionReferences |
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One of the problems encountered when treating ARDS in a patient already addicted to narcotics and benzodiazepines is the withdrawal process itself. For the patient to tolerate the endotracheal tube for extended periods, he or she must be kept sedated and comfortable. For critically ill patients, lorazepam is the preferred drug for prolonged treatment of anxiety, and fentanyl is recommended for acutely distressed patients with hemodynamic instability (1). Unfortunately, the drugs of choice for this patient’s therapy were similar to his drugs of abuse. When his respiratory condition had improved sufficiently that ventilator assistance was no longer medically necessary, benzodiazepine and opioid withdrawal became the limiting factor in his recovery. Propofol did not allay his anxiety or control the withdrawal symptoms.
Hypertension, anxiety, agitation, tachycardia, and fever occurring during benzodiazepine and opioid withdrawal are attenuated by the 2 agonists (2–4) . Withdrawal from narcotics is characterized by a hypernoradrenergic state. The 2-adrenoceptor agonists decrease sympathetic outflow and noradrenergic activity, counteracting the physiologic effects of withdrawal rather than acting as a substitute for the drug being withdrawn (5). These effects are largely mediated by the postsynaptic 2A receptor subtype in the locus caeruleus (6–8) . Reduced sympathetic tone and increased parasympathetic tone reduce metabolism, heart rate, myocardial contractility, and vascular resistance. These effects reduce myocardial oxygen requirements (9). Clonidine has been used to attenuate the symptoms of withdrawal from narcotics and naloxone-induced hypertension for more than 20 years (10–12) . Dexmedetomidine has a higher affinity for the 2A receptors than clonidine, resulting in more selective 2A activation and less of the deleterious 1 stimulation (13).
Opiates and 2 agonists act synergistically on central sympathetic outflow (14). The potentiating effects of the 2 agonists on morphine reduce the amount of opioid needed and how long a fixed dose of the opioid is effective (15). The mechanism by which dexmedetomidine enhances the analgesic effects of morphine is not clear. There is some evidence that 2 agonist-induced antinociception results from acetylcholine release inhibiting nociceptive neurons in the spinal cord (9).
A major advantage of dexmedetomidine over other sedatives is respiratory stability (16,17) . A patient can be maintained at a Ramsay sedation level of 2–4 on a continuous infusion during weaning and extubation without depression of the respiratory drive. The characteristic effects of dexmedetomidine relieve anxiety, reduce opioid needs, and facilitate conscious sedation (9). Dexmedetomidine also blunts the effects of cocaine (4). In this case, dexmedetomidine attenuated the symptoms of withdrawal, allowing a smooth transition off the ventilator and the lorazepam and fentanyl infusions.
Two clinical studies were recently published in which dexmedetomidine was used for up to seven days in the medical ICU (18,19) . Hemodynamic stability was preserved, with no myocardial depression and no rebound effect on withdrawal.
In the case described here, dexmedetomidine facilitated withdrawal from lorazepam and fentanyl. With no risk of respiratory depression, conscious sedation was maintained throughout weaning and extubation. The symptoms of withdrawal were relieved without delaying weaning.
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References |
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- Jacobi J, Fraser GL, Coursin DB, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med 2002; 30: 119–41.[Web of Science][Medline]
- Shafer A. Complications of sedation with midazolam in the intensive care unit and a comparison with other sedative regimens. Crit Care Med 1998; 26: 947–56.[Web of Science][Medline]
- Ghignone M, Quintin L, Duke PC, et al. Effects of clonidine on narcotic requirements and hemodynamic response during induction of fentanyl anesthesia and endotracheal intubation. Anesthesiology 1986; 64: 36–42.[Web of Science][Medline]
- Kersten JR, Pagel PS, Hettrick DA, Warltier DC. Dexmedetomidine partially attenuates the sympathetically mediated systemic and coronary hemodynamic effects of cocaine. Anesth Analg 1995; 80: 114–21.[Abstract]
- Maze M, Segal IS, Bloor BC. Clonidine and other alpha-2 adrenergic agonists: strategies for the rational use of these novel anesthetic agents. J Clin Anesth 1988; 1: 146–57.[Medline]
- Coupar IM. Effect of alpha-2 adrenoceptor agonists on the expression of morphine withdrawal in rats. Naunyn Schmiedebergs Arch Pharmacol 1992; 345: 553–7.[Web of Science][Medline]
- Lidbrink P. The effect of lesions of ascending noradrenaline pathways on sleep and waking in the rat. Brain Res 1974; 74: 19–40.[Web of Science][Medline]
- Glass MJ, Pickel VM. Alpha(2A)-adrenergic receptors are present in mu-opioid receptor containing neurons in rat medial nucleus tractus solitarius. Synapse 2002; 43: 208–18.[Web of Science][Medline]
- Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists: their pharmacology and therapeutic role. Anaesthesia 1999; 54: 146–65.[Web of Science][Medline]
- Aley KO, Levine JD. Dissociation of tolerance and dependence for opioid peripheral antinociception in rats. J Neurosci 1997; 17: 3907–12.
[Abstract/Free Full Text] - Ashton H. Benzodiazepine withdrawal: outcome in 50 patients. Br J Addict 1987; 82: 665–71.[Web of Science][Medline]
- Milne B. Alpha-2 agonists and anaesthesia. Can J Anaesth 1991; 38: 809–13.[Web of Science][Medline]
- Tella SR, Korupolu GR, Schindler CW, Goldberg SR. Pathophysiological and pharmacological mechanisms of acute cocaine toxicity in conscious rats. J Pharmacol Exp Ther 1992; 262: 936–46.
[Abstract/Free Full Text] - Maze M, Virtanen R, Daunt D, et al. Effects of dexmedetomidine, a novel imidazole sedative-anesthetic agent, on adrenal steroidogenesis: in vivo and in vitro studies. Anesth Analg 1991; 73: 204–8.
[Abstract/Free Full Text] - Meert TF, De Kock M. Potentiation of the analgesic properties of fentanyl-like opioids with alpha 2-adrenoceptor agonists in rats. Anesthesiology 1994; 81: 677–88.[Web of Science][Medline]
- Hall JE, Uhrich TD, Barney JA, et al. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg 2000; 90: 699–705.
[Abstract/Free Full Text] - Venn RM, Hell J, Grounds RM. Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care. Crit Care 2000; 4: 302–8.[Web of Science][Medline]
- Venn RM, Newman P, Grounds RM. A phase II study to evaluate the safety and cardiovascular effects of dexmedetomidine for sedation in the medical intensive care unit. Intensive Care Med. In press.
- Riker RR, Ramsay MAE, Prielipp RC, Jorden V. Long-term dexmedetomidine infusions for ICU sedation: a pilot study [abstract]. Anesthesiology 2001; 95: A383.
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