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  • Good evening everybody. At the outset, I would like to thank you all for sparing your valuable time for this CME on DXMD DXMD, i.e. Dexmedetomidine Hydrochloride, the sedative that ensures patient comfort and safety
  • The intensive care unit (ICU) is a frightening place for a common man. Patients are surrounded by machines and are attached to various equipment via tubes and wires. The sight, even the thought of ICU creates fear and ANXIETY in the mind of a healthy onlooker. Then what might be happening to the critically ill patient who are confined to the bed , and may be intubated and ventilated. No doubt these Critically ill patients, especially those who are conscious, suffer from sever anxiety / fear, far beyond what their bedside caregivers can appreciate. This pathological ANXIETY add to the stress already caused by the disease and the therapy themselves .
  • Anxiety & Agitation are an important causes of stress. Critically ill patients usually also have feelings of helplessness, loss of control, disorientation, and panic. Even ICU survivors may sustain a type of posttraumatic stress syndrome for many months or years. Anxiety arises from an innate sense of life-threatening illness, from strange surroundings found in the ICU environment, from an inability to communicate effectively, from sleep deprivation and from the squad of healthcare personnel that shuttles in and out of the patient's room 24 hours per day. This fear and ANXIETY in the patient add to the stress already caused by the disease and the therapy themselves . (Semin Respir Crit Care Med. 2001;22(2):165-74 )
  • The heightened stress induces a neuro-endocrine response characterised by  sympathetic activity,  levels of Adrenaline, ACTH, GH, Aldosterone, release of cytokines  inflammatory response . The stress response contributes to hyperglycemia, increased metabolism, and increased oxygen demand. Stress includes physiological, chemical, pharmacological, emotional, and environmental factors that may lead to physical and psychological exhaustion interfering with patients’ ability to recover. This neuroendocrine cascade leads to increased oxygen consumption, increased carbon dioxide production, and a generalized catabolic state with a negative nitrogen balance
  • Hence, sedation is necessary in these patients to Reduce anxiety Facilitate mechanical ventilation. Induce sleep when required Avoid or reduce delirium Attenuate the harmful adrenergic response Induce appropriate level of amnesia and prevent post-ICU psychosis Facilitate patient’s communication with caregivers and family members To improve patient comfort
  • Sedation is a continuum. The levels on this continuum are: Minimal sedation (anxiolysis) Moderate sedation/analgesia (“formerly conscious sedation”) Deep sedation/analgesia General Anesthesia Why is it important to understand the continuum of sedation? Because the response of any one patient may be unpredictable. For example, a patient may be moderately sedated for a procedure. However, the patient may respond to the drug in an unexpected way, and enter a state of deep sedation instead. Moderate sedation does not usually put a patient’s breathing or heart function at risk. But a moderately sedated patient may progress to deep sedation. Therefore, moderate sedation must be monitored just as carefully as deep sedation and anesthesia.
  • Figure 1. Conceptual framework for the interactions among underlying and causative factors, the sensations of pain, anxiety, and delirium, pharmacologic and nonpharmacologic interventions, and the state of a patient along the continuum from deep sedation to overt agitation. (CHEST 2008; 133:552–565) 50 % - 70% patients in ICU receive some form of sedation and analgesia during their stay. ( J Anesth Clin Pharmacology 2007; 23(3): 241-247)
  • Most useful during procedures in which communication with the patient must be maintained 1 Patient easily transitions from sleep to wakefulness and task performance when aroused 1 Patient is able to resume rest when not stimulated 1 Allows for Accurate evaluation of the Neuropsychological status of patients 1 Patient’s interaction in care decisions 2 Facilitates participation in therapeutic maneuvers 2 http://health.enotes.com/medicine-encyclopedia/sedation 1-Bekker AY, et al. Neurosurgery. 2005;57(1 Suppl 1):1-10. 2-Burns AM, et al. Drugs . 1992;43:507-515.
  • Current choices for sustained sedation in the critically ill include the benzodiazepines (amnesia) the opiates (analgesia) Propofol (easily titratable and less likely to accumulate) (Semin Respir Crit Care Med. 2001;22(2):165-74)
  • Route: Intravenous infusion (recommended route) Loading: 1mcg/kg over 10 min Maintenance: 0.2-0.7 mcg/kg/hr Half Life: Short distribution half-life (6 min): Rapid onset of sedation Short elimination half-life (2 hr): Facilitates clearance Fast distribution & short elimination half life is ideal for an intravenous drug. Protein binding: 94% Metabolized in liver almost completely Elimination: Renal excretion
  • Dexmedetomidine and stage of sleep: Dexmedetomidine produces a state closely resembling physiological Stage 2 Non Rapid Eye Movement sleep in humans. Due to this patients who are asleep after Dexmedetomidine administration can be easily awakened. This offers considerable advantage over currently used agents that often patients render the patient non-responsive or semi-anaesthetized. Acta Anaesthesiol Scand 2008; 52: 289–294
  • Arousal: A tonic inhibitory noradrenergic impulse from Locus coeruleus (LC) inhibits the ventrolateral preoptic nucleus (VLPO) thus reduces the release of GABA from VLPO into the tuberomammillary nucleus (TMN). In absence of this GABA-ergic inhibition, the TMN release arousal-promoting histamine into the cortex and forebrain and stimulates the cortex leading to awakening. NREM sleep: ( Apart from other pathways initiating sleep) A decrease in the activity of the LC releases (disinhibits) the “sleep-promoting” GABA-ergic neurons in the VLPO which inhibits the TMN and reduce the release arousal-promoting histamine. This reduces cortical stimulation and sleep is initiated. Dexmedetomidine decreases in the activity in the LC and initiates a sleep similar to natural NREM sleep (Anesthesiology 2003; 98:428-36; attached).
  • INTRODUCTION: Most anxiolytics and sedative regimens in the intensive care unit (ICU) impair intellectual function, reducing patient autonomy, and often add to patient morbidity. Using an ICU-validated cognitive assessment tool Adapted Cognitive Exam (ACE), we performed a comparison between dexmedetomidine (DEX) and propofol (PRO) to evaluate which sedative regimen offered the least decrement in intellectual capacity. METHODS: This was a prospective, randomized, double-blinded study of 30 awake and intubated brain-injured (BI, n = 18) and non-BI (12) ICU patients. Each patient received fentanyl/PRO and fentanyl/DEX titrated to a calm, awake state using a crossover design. Cognitive testing was performed at each study period using the validated 100-point Hopkins ACE cognitive battery. FINDINGS: Sedation with PRO diminished adjusted ACE scores (100-point exam) by a mean of -12.4 (95% CI -8.3 to -16.5, p < 0.001) while DEX, in contrast, improved ACE scores (6.8, 95% CI 1.2-12.4, p < 0.018). The difference in the change of ACE score between DEX versus PRO, our primary endpoint, was 19.2 (95% CI 12.3-26.1 p < 0.001) in favor of an improved ACE score on DEX. Patients with BI required less sedative, but effects of PRO and DEX on cognition were not changed. No serious adverse events occurred. Modest bradycardia was noted post hoc with DEX (-7.7 bpm, p < 0.01). INTERPRETATION: ICU patients may be offered sedation without necessarily compromising arousal or cognition. Alleviation of anxiety and agitation can singly and effectively improve mental engagement and performance if overt forebrain dysfunction is avoided. Higher ACE scores with DEX may be a consequence of the intellect-sparing yet calming effect of this drug.
  • SEDCOM (Safety and Efficacy of Dexmedetomidine COmpared With Midazolam). Objective To compare the efficacy and safety of prolonged sedation with dexmedetomidine vs midazolam for mechanically ventilated patients. Design, Setting, and Patients Prospective, double-blind, randomized trial conducted in 68 centers in 5 countries between March 2005 and August 2007 among 375 medical/surgical ICU patients with expected mechanical ventilation for more than 24 hours. Sedation level and delirium were assessed using the Richmond Agitation- Sedation Scale (RASS) and the Confusion Assessment Method for the ICU. Interventions Dexmedetomidine (0.2-1.4 μg/kg per hour [n=244]) or midazolam (0.02-0.1 mg/kg per hour [n=122]) titrated to achieve light sedation (RASS scores between −2 and 1) from enrollment until extubation or 30 days. Main Outcome Measures Percentage of time within target RASS range. Secondary end points included prevalence and duration of delirium, use of fentanyl and openlabel midazolam, and nursing assessments. Additional outcomes included duration of mechanical ventilation, ICU length of stay, and adverse events. Results There was no difference in percentage of time within the target RASS range (77.3% for dexmedetomidine group vs 75.1% for midazolam group; difference, 2.2% [95% confidence interval {CI}, −3.2% to 7.5%]; P =.18). The prevalence of delirium during treatment was 54% (n=132/244) in dexmedetomidinetreated patients vs 76.6% (n=93/122) in midazolam-treated patients (difference, 22.6% [95% CI, 14% to 33%]; P .001). Median time to extubation was 1.9 days shorter in dexmedetomidine-treated patients (3.7 days [95% CI, 3.1 to 4.0] vs 5.6 days [95% CI, 4.6 to 5.9]; P =.01), and ICU length of stay was similar (5.9 days [95% CI, 5.7 to 7.0] vs 7.6 days [95% CI, 6.7 to 8.6]; P =.24). Dexmedetomidinetreated patients were more likely to develop bradycardia (42.2% [103/244] vs 18.9% [23/122]; P .001), with a nonsignificant increase in the proportion requiring treatment (4.9% [12/244] vs 0.8% [1/122]; P =.07), but had a lower likelihood of tachycardia (25.4% [62/244] vs 44.3% [54/122]; P .001) or hypertension requiring treatment (18.9% [46/244] vs 29.5% [36/122]; P =.02). Conclusions There was no difference between dexmedetomidine and midazolam in time at targeted sedation level in mechanically ventilated ICU patients. At comparable sedation levels, dexmedetomidine-treated patients spent less time on the ventilator, experienced less delirium, and developed less tachycardia and hypertension. The most notable adverse effect of dexmedetomidine was bradycardia. JAMA. 2009;301(5):489-499
  • SEDCOM (Safety and Efficacy of Dexmedetomidine COmpared With Midazolam). Objective To compare the efficacy and safety of prolonged sedation with dexmedetomidine vs midazolam for mechanically ventilated patients. Design, Setting, and Patients Prospective, double-blind, randomized trial conducted in 68 centers in 5 countries between March 2005 and August 2007 among 375 medical/surgical ICU patients with expected mechanical ventilation for more than 24 hours. Sedation level and delirium were assessed using the Richmond Agitation- Sedation Scale (RASS) and the Confusion Assessment Method for the ICU. Interventions Dexmedetomidine (0.2-1.4 μg/kg per hour [n=244]) or midazolam (0.02-0.1 mg/kg per hour [n=122]) titrated to achieve light sedation (RASS scores between −2 and 1) from enrollment until extubation or 30 days. Main Outcome Measures Percentage of time within target RASS range. Secondary end points included prevalence and duration of delirium, use of fentanyl and openlabel midazolam, and nursing assessments. Additional outcomes included duration of mechanical ventilation, ICU length of stay, and adverse events. Results There was no difference in percentage of time within the target RASS range (77.3% for dexmedetomidine group vs 75.1% for midazolam group; difference, 2.2% [95% confidence interval {CI}, −3.2% to 7.5%]; P =.18). The prevalence of delirium during treatment was 54% (n=132/244) in dexmedetomidinetreated patients vs 76.6% (n=93/122) in midazolam-treated patients (difference, 22.6% [95% CI, 14% to 33%]; P .001). Median time to extubation was 1.9 days shorter in dexmedetomidine-treated patients (3.7 days [95% CI, 3.1 to 4.0] vs 5.6 days [95% CI, 4.6 to 5.9]; P =.01), and ICU length of stay was similar (5.9 days [95% CI, 5.7 to 7.0] vs 7.6 days [95% CI, 6.7 to 8.6]; P =.24). Dexmedetomidinetreated patients were more likely to develop bradycardia (42.2% [103/244] vs 18.9% [23/122]; P .001), with a nonsignificant increase in the proportion requiring treatment (4.9% [12/244] vs 0.8% [1/122]; P =.07), but had a lower likelihood of tachycardia (25.4% [62/244] vs 44.3% [54/122]; P .001) or hypertension requiring treatment (18.9% [46/244] vs 29.5% [36/122]; P =.02). Conclusions There was no difference between dexmedetomidine and midazolam in time at targeted sedation level in mechanically ventilated ICU patients. At comparable sedation levels, dexmedetomidine-treated patients spent less time on the ventilator, experienced less delirium, and developed less tachycardia and hypertension. The most notable adverse effect of dexmedetomidine was bradycardia. JAMA. 2009;301(5):489-499
  • (DEXCOM Study: DEXmedetomidine COmpared to Morphine) Background: Commonly used sedatives/analgesics can increase the risk of postoperative complications, including delirium. This double-blinded study assessed the neurobehavioral, hemodynamic, and sedative characteristics of dexmedetomidine compared with morphine-based regimen after cardiac surgery at equivalent levels of sedation and analgesia. Methods: A total of 306 patients at least 60 yr old were randomized to receive dexmedetomidine (0.1– 0.7mcg · kg1 ·h1) or morphine (10-70 mcg · kg1 · h1) with open-label propofol titrated to a target Motor Activity Assessment Scale of 2–4. Primary outcome was the prevalence of delirium measured daily via Confusion Assessment Method for intensive care. Secondary outcomes included ventilation time, additional sedation/analgesia, and hemodynamic and adverse effects. Results: Of all sedation assessments, 75.2% of dexmedetomidine and 79.6% ( P 0.516) of morphine treatment were in the target range. Delirium incidence was comparable between dexmedetomidine 13 (8.6%) and morphine 22 (15.0%) (relative risk 0.571, 95% confidence interval [CI] 0.256–1.099, P 0.088), however, dexmedetomidine-managed patients spent 3 fewer days (2 [1–7] versus 5 [2–12]) in delirium (95% CI 1.09–6.67, P 0.0317). The incidence of delirium was significantly less in a small subgroup requiring intraaortic balloon pump and treated with dexmedetomidine (3 of 20 [15%] versus 9 of 25 [36%]) (relative risk 0.416, 95% CI 0.152–0.637, P 0.001). Dexmedetomidine-treated patients were more likely to be extubated earlier (relative risk 1.27, 95% CI 1.01–1.60, P 0.040, log-rank P 0.036), experienced less systolic hypotension (23% versus 38.1%, P 0.006), required less norepinephrine ( P < 0.001), but had more bradycardia (16.45% versus 6.12%, P 0.006) than morphine treatment. Conclusion: Dexmedetomidine reduced the duration but not the incidence of delirium after cardiac surgery with effective analgesia/sedation, less hypotension, less vasopressor requirement, and more bradycardia versus morphine regimen. Anesthesiology 2009; 111:1075–84
  • In this study prolonged Dexmedetomidine infusion was evaluated in critically ill infants and children. Twenty-nine patients aged about 6 years old participated in this study. Dexmedetomidine was administered at dose of 0.1-1.5 µg/kg/hour for 110 hours. Dexmedetomidine infusion was slowly tapered downward as therapy was ending. In general, 25-50% dose reductions were made per day. The above graph shows that after starting Dexmedetomidine administration 54% of the patient discontinued opioids therapy and 45% of the patient discontinued benzodiazepines therapy. This study showed that Prolonged Dexmedetomidine infusion in critically ill infants and children was associated with a reduction in concomitant analgesia and sedation medications.
  • BACKGROUND: Agitation is associated with failure of noninvasive ventilation (NIV). We investigated the effect of dexmedetomidine in patients with NIV. METHODS: This was a prospective clinical investigation in an intensive care unit. Dexmedetomidine was infused in 10 patients in whom NIV was difficult because of agitation. RESULTS: Ramsay and Richmond Agitation-Sedation Scale scores were maintained at 2.94 0.94 and 1.23 1.30, respectively. All patients were successfully weaned from NIV, and the respiratory state was not worsened. CONCLUSION: This study shows that dexmedetomidine is an effective sedative drug for patients with NIV. (Anesth Analg 2008;107:167–70)
  • BACKGROUND: In clinical practice, new drugs may be used differently than the product labeling recommends. Furthermore, it often takes several years of use before adverse drug reactions (ADRs) are reported. OBJECTIVE: To compare prescribing patterns and safety of the newly released drug dexmedetomidine as observed in clinical practice with published data on the drug. METHODS: Information from a convenience sample of adults receiving dexmedetomidine as part of routine patient care at 10 institutions was retrospectively collected from June 27, 2001, to May 31, 2002. Investigators reviewed medical records daily and entered dosing information, patient demographics, and predefined categories of ADR severity and probability anonymously via the Internet on a secure server. RESULTS: Only 33% of the total sample (n = 136) of patients received a loading infusion of dexmedetomidine; however, maintenance dosing was usually within product labeling guidelines. Of note, 27.2% of patients received dexmedetomidine above the maximum dose and 33.8% received the drug beyond 24 hours. Some patients (15.4%) were never mechanically ventilated, while 59.5% received dexmedetomidine following extubation for an average of 11.3 hours. ADRs were reported in 30% of patients: 20% of the reactions required treatment or increased length of stay. Hypotension was the most common ADR, occurring in 22.7% of patients. Bradycardia was reported in 4.4% of patients. The rate and type of ADRs were similar in patients receiving dexmedetomidine >24 hours compared with the total population. CONCLUSIONS: Dexmedetomidine is prescribed within product labeling guidelines except for low use of a loading dose, some patients received the drug at doses above the maximum, and others received it for longer than 24 hours. Since ADR rates are similar to those of other published reports, dexmedetomidine maintained its expected safety profile in our patients. Ann Pharmacother. 2004 Jul-Aug;38(7-8):1130-5.
  • Salina Regional Health Center, Kansas, is a 200-bed regional medical center with a 12-bed general medical-surgical ICU. Previously, propofol was the primary drug for sedation. Midazolam was used occasionally if a patient had an allergy to propofol or another medical reason the drug could not be used. The types of patients who commonly received propofol included postoperative patients and patients who had respiratory failure or sepsis. The dissatisfaction associated with oversedation that commonly occurs with propofol and other sedative agents led to the consideration of experimenting with exmedetomidine. Other problems encountered with the use of propofol included the daily wake-up not being performed, disorientation or delirium with prolonged use (>48 hours), and the excessive amount of calories associated with high rates of propofol administration. Total ICU days were 1686 before DXMD use (October 2006 through May 2007) and 1414 after DXMD use (October 2007 through May 2008), a 19% decrease (272 fewer days) in total ICU days ( P = .05). Mean length of stay decreased from 2.34 days to 2.31 days (1.5% reduction; P = .05). All of these results are statistically significant . This study showed that dexmedetomidine can help reduce duration of mechanical ventilation and number of days in the ICU.
  • Intensive care unit (ICU) delirium, a form of acute brain dysfunction, is a lifethreatening global disturbance of cognitive function that is highly prevalent in critically ill patients, especially the elderly and patients requiring sedation for mechanical ventilation.[1] ICU delirium is reported to occur in up to 85% of critically ill patients.[2,3] The current standard of care for sustained sedation in this patient population is the use of a combination of agents, including propofol, opioids, and the benzodiazepines lorazepam and midazolam.[4,5] When used in combination, these agents can be associated with a number of Benzodiazepines, however, are associated with acute brain dysfunction (ICU delirium), which contributes to prolonged hospital length of stay, cost, and increased mortality. BDZs (lorazepam and midazolam) are associated with worse clinical outcomes, including a greater risk for development of delirium or brain dysfunction. http://www.medscape.com/viewarticle/581995 MENDS trial: Context Lorazepam is currently recommended for sustained sedation of mechanically ventilated intensive care unit (ICU) patients, but this and other benzodiazepine drugs may contribute to acute brain dysfunction, ie, delirium and coma, associated with prolonged hospital stays, costs, and increased mortality. Dexmedetomidine induces sedation via different central nervous system receptors than the benzodiazepine drugs and may lower the risk of acute brain dysfunction. Objective To determine whether dexmedetomidine reduces the duration of delirium and coma in mechanically ventilated ICU patients while providing adequate sedation as compared with lorazepam. MENDS trial. JAMA 2007;298(22):2644-2653
  • Design, Setting, Patients, and Intervention Double-blind, randomized controlled trial of 106 adult mechanically ventilated medical and surgical ICU patients at 2 tertiary care centers between August 2004 and April 2006. Patients were sedated with dexmedetomidine or lorazepam for as many as 120 hours. Study drugs were titrated to achieve the desired level of sedation, measured using the Richmond Agitation- Sedation Scale (RASS). Patients were monitored twice daily for delirium using the Confusion Assessment Method for the ICU (CAM-ICU). Main Outcome Measures Days alive without delirium or coma and percentage of days spent within 1 RASS point of the sedation goal. Results Sedation with dexmedetomidine resulted in more days alive without delirium or coma (median days, 7.0 vs 3.0; P =.01) and a lower prevalence of coma (63% vs 92%; P .001) than sedation with lorazepam. Patients sedated with dexmedetomidine spent more time within 1 RASS point of their sedation goal compared with patients sedated with lorazepam (median percentage of days, 80% vs 67%; P =.04). The 28-day mortality in the dexmedetomidine group was 17% vs 27% in the lorazepam group ( P =.18) and cost of care was similar between groups. More patients in the dexmedetomidine group (42% vs 31%; P =.61) were able to complete post-ICU neuropsychological testing, with similar scores in the tests evaluating global cognitive, motor speed, and attention functions. The 12-month time to death was 363 days in the dexmedetomidine group vs 188 days in the lorazepam group ( P =.48). Conclusion In mechanically ventilated ICU patients managed with individualized targeted sedation, use of a dexmedetomidine infusion resulted in more days alive without delirium or coma and more time at the targeted level of sedation than with a lorazepam infusion. MENDS trial. JAMA 2007;298(22):2644-2653
  • Dexmedetomidine and the Reduction of Postoperative Delirium after Cardiac Surgery Background: Delirium is a neurobehavioral syndrome caused by the transient disruption of normal neuronal activity secondary to systemic disturbances. Objective: The authors investigated the effects of postoperative sedation on the development of delirium in patients undergoing cardiac-valve procedures. Methods: Patients underwent elective cardiac surgery with a standardized intraoperative anesthesia protocol, followed by random assignment to one of three postoperative sedation protocols: dexmedetomidine, propofol, or midazolam. Results: The incidence of delirium for patients receiving dexmedetomidine was 3%, for those receiving propofol was 50%, and for patients receiving midazolam, 50%. Patients who developed postoperative delirium experienced significantly longer intensive-care stays and longer total hospitalization. Conclusion: The findings of this open-label, randomized clinical investigation suggest that postoperative sedation with dexmedetomidine was associated with significantly lower rates of postoperative delirium and lower care costs. ( Psychosomatics 2009; 50:206 –217)
  • Dexmedetomidine and the Reduction of Postoperative Delirium after Cardiac Surgery Background: Delirium is a neurobehavioral syndrome caused by the transient disruption of normal neuronal activity secondary to systemic disturbances. Objective: The authors investigated the effects of postoperative sedation on the development of delirium in patients undergoing cardiac-valve procedures. Methods: Patients underwent elective cardiac surgery with a standardized intraoperative anesthesia protocol, followed by random assignment to one of three postoperative sedation protocols: dexmedetomidine, propofol, or midazolam. Results: The incidence of delirium for patients receiving dexmedetomidine was 3%, for those receiving propofol was 50%, and for patients receiving midazolam, 50%. Patients who developed postoperative delirium experienced significantly longer intensive-care stays and longer total hospitalization. Conclusion: The findings of this open-label, randomized clinical investigation suggest that postoperative sedation with dexmedetomidine was associated with significantly lower rates of postoperative delirium and lower care costs. ( Psychosomatics 2009; 50:206 –217)
  • Anxiety, fear and agitation are amongst the most common non-pulmonary causes of failure to liberate from mechanical ventilation. Ventilated patients receiving opioids and/or BDZs are at high risk of developing agitation, particularly upon weaning towards extubation. Agitated patients can NOT be easily weaned off ventilation (on propofol, midazolam, lorazepam, narcotics). This is often associated with an increased intubation time and length of stay in the ICU and may cause long-term morbidity.
  • The effect of dexmedetomidine on agitation during weaning of mechanical ventilation in critically ill patients. Abstract Ventilated patients receiving opioids and/or benzodiazepines are at high risk of developing agitation, particularly upon weaning towards extubation. This is often associated with an increased intubation time and length of stay in the intensive care unit and may cause long-term morbidity. Anxiety, fear and agitation are amongst the most common non-pulmonary causes of failure to liberate from mechanical ventilation. This prospective, open-label observational study examined 28 ventilated adult patients in the intensive care unit (30 episodes) requiring opioids and/or sedatives for >24 hours, who developed agitation and/or delirium upon weaning from sedation and failed to achieve successful extubation with conventional management. Patients were ventilated for a median (interquartile range) of 115 [87 to 263] hours prior to enrolment. Dexmedetomidine infusion was commenced at 0.4 microg/kg/hour for two hours, after which concurrent sedative therapy was preferentially weaned and titrated to obtain target Motor Activity Assessment Score score of 2 to 4. The median (range) maximum dose and infusion time of dexmedetomidine was 0.7 microg/kg/hour (0.4 to 1.0) and 62 hours (24 to 252) respectively. The number of episodes at target Motor Activity Assessment Score score at zero, six and 12 hours after commencement of dexmedetomidine were 7/30 (23.3%), 28/30 (93.3%) and 26/30 (86.7%), respectively (P < 0.001 for 6 and 12 vs. 0 hours). Excluding unrelated clinical deterioration, 22 episodes (73.3%) achieved successful weaning from ventilation with a median (interquartile range) ventilation time of 70 (28 to 96) hours after dexmedetomidine infusion. Dexmedetomidine achieved rapid resolution of agitation and facilitated ventilatory weaning after failure of conventional therapy. Its role as first-line therapy in ventilated, agitated patients warrants further investigation. Anaesth Intensive Care. 2010 Jan;38(1):82-90.
  • Clinicians often transition patients who have been on other IV sedatives to dexmedetomidine-based sedation in preparation for weaning and extubation. In such patients, an infusion of dexmedetomidine without a loading should be started at 0.4 μg/kg/hr for 2 hours before stopping other sedative medications. Concurrent sedative and/or narcotic therapy can then be preferentially weaned 2 hours after initiating dexmedetomidine infusion . The dexmedetomidine dose can be titrated by 0.2 μg/kg/hr every 30 minutes to the maximum desired dose to achieve light sedation (‘responsive to touch or name’, ‘calm and cooperative’ or ‘restless but cooperative’). Rescue sedation (midazolam 1 mg and/or propofol 25-30 mg) can be given episodes of agitation. Other ICU interventions should continue as clinically indicated. Additional analgesia can be given as (1-2 mg morphine or 10-20 µg fentanyl) if required. Ventilator weaning should continue as clinically appropriate. Dexmedetomidine infusion can be discontinued once no longer required, at the discretion of the treating physician. (Crit Care & Shock (2010) 13:40-50)
  • Transitioning of IV sedation to dexmedetomidine ( Figure 3 ) Clinicians often transition patients who have been on other IV sedatives to dexmedetomidine based sedation in preparation for weaning and extubation. In such patients, an infusion of dexmedetomidine without a loading should be started at 0.4 μg/kg/hr for 2 hours before stopping other sedative medications. Concurrent sedative and/or narcotic therapy can then be preferentially weaned 2 hours after initiating dexmedetomidine infusion. The dexmedetomidine dose can be titrated by 0.2 μg/kg/hr every 30 minutes to the maximum desired dose to achieve light sedation (‘responsive to touch or name’, ‘calm and cooperative’ or ‘restless but cooperative’). Rescue sedation (midazolam 1 mg and/or propofol 25-30 mg) can be given episodes of agitation. Other ICU interventions should continue as clinically indicated. Additional analgesia can be given as (1-2 mg morphine or 10-20 μg fentanyl) if required. Ventilator weaning should continue as clinically appropriate. Dexmedetomidine infusion can be discontinued once no longer required, at the discretion of the treating physician.
  • Comparison of Dexdine vs. other Sedative Analgesics used in ICU References: Crit Care Nurse. 2010;30: 29-38 Crticial Care 2009 vol 13 no 3 Drugs 2000 Feb; 59(2):263-268 Goodman Gilman 11th edition A Live Educational Activity, Targeting sedation & analgesia: Sponsored by the Academy for Continued Healthcare Learning & Educational Grant from Hospira. J Anesth Clin Pharmacology 2007; 23 (3): 241-247 Procedural Sedation.emedicine.medscape.com JAMA December 12, 2007, 298(22); 2644-2653
  • Comparison of Dexdine vs. other Sedative Analgesics used in ICU References: Crit Care Nurse. 2010;30: 29-38 Crticial Care 2009 vol 13 no 3 Drugs 2000 Feb; 59(2):263-268 Goodman Gilman 11th edition A Live Educational Activity, Targeting sedation & analgesia: Sponsored by the Academy for Continued Healthcare Learning & Educational Grant from Hospira. J Anesth Clin Pharmacology 2007; 23 (3): 241-247 Procedural Sedation.emedicine.medscape.com JAMA December 12, 2007, 298(22); 2644-2653
  • Sedative in ICU The current standard of care, to facilitate a patient's adaptation to mechanical ventilation, is the use of a combination of agents including propofol, opioids, and benzodiazepines which can be associated with a number of side effects, particularly respiratory depression, especially when agents are used concurrently. Dexmedetomidine as a Primary Sedative in ICU Dexmedetomidine, as a single agent, produces sedation, analgesia, anxiolysis, stable respiratory rates, and predictable cardiovascular responses. It seems to have a potential to be used as first line drug in ICU sedation. Other agents (opioids, benzodiazepines and/or propofol) may be added as and when required.
  • ICU Sedation Dexmedetomedine is indicated for sedation in intubated and mechanically ventilated patients . Dexmedetomidine should be administered by continuous infusion not to exceed 24 hours. Dexmedetomedine can be administered by continuously infusion in mechanically ventilated patients prior to extubation, during extubation, and post-extubation . It is not necessary to discontinue Dexmedetomedine prior to extubation . Procedural Sedation Dexmedetomedine is indicated for sedation of non-intubated patients prior to and/ or during surgical and other procedures.
  • Off Label Use: Not approved by the concerned regulatory authority, but widely used by doctors
  • A. Infusions should always start at 0.4 µg/kg/hr for one hour and be increased thereafter as required. Assessment of sedation and pain scales should be performed as part of ongoing evaluation at least every 4 hours. B. The maximum dose above 1 µg/kg/hr is not identified or approved. However, according to published literature, it is reasonable to use a dose up to 1.5 µg/kg/hr. C. This can be achieved by adjusting the volume of 5%DW or N/S added to 200 µg (full vials of dexmedetomidine) so that every ml contains 0.1 µg/kg of dexmedetomidine. This will also avoid discarding any dexmedetomidine, thereby avoiding any wastage. NB: Additional sedation and analgesia should be kept to a minimum but can be given as described above in the text and guided by sedation targets and the adequacy of pain relief. Sedation advisory board in Intensive Care, Prince of Wales Hospital, Australia
  • High risk complex surgical patients Typical patients in this category include those with: 1. Compromised respiratory function due to chronic airways disease. 2. Difficult airway and sleep apnoea, particularly in obese patients. 3. Anxiety and apprehension 4. A history of delirium following previous operations 5. Narcotic intolerance or history of abuse 6. A critical need for cardiovascular stability, in particular the avoidance of blood pressure swings, such as after thoracic aneurysm repair or aortic valve replacement 7. Elderly patients
  • Refractory haemodynamic instability, including: Systolic blood pressure of less than 90mmHg or a mean BP less than 60 mmHg despite significant vasopressor support, such as vasopressin > 2 units per hour or noradrenaline or adrenaline > 0.2 µg/kg/min or dobutamine > 10 µg/kg/min. Heart rate less than 55 beats per minute, not induced by beta-blocking agents. High grade atrioventricular block in the absence of pace maker.
  • Ensuring sedation and analgesia with optimization of patient communication in patients in critical care is difficult with currently available agents. Dexdine, as a single agent, produces conscious sedation, anxiolysis and analgesia, reduces delirium and agitation, without respiratory depression and with predictable and desirable cardiovascular effects. Dexdine also reduces the anesthetic and analgesic requirements. Dexdine appears to be a better alternative to the conventional strategy of sedation and analgesia utilizing benzodiazepines, opiates and propofol. Addition of DXMD to the current standard of care would ensure improved clinical outcomes, reduced total hospital costs and ensure patient comfort
  • Pharmacologic Agents Used for the Sedative and Analgesic Management of ICU Patients Module 3 The first surgeries i used dex in were morbidly obese patients w sleep apnea- dex allowed me to dec the opioids + get the tracheal tube out early + safely- cooperative with a sedated pain free patient w/o resp depression The next series of pts i used dex for were the crani for aneurysm- we use hypothermia to 33 C, + dex really helps prevent shivering during rewarming while at the same time allowing for a cooperative pt to do neuro exams on. then i started w cervical spine surgery- again for the smooth emergence.
  • Pharmacologic Agents Used for the Sedative and Analgesic Management of ICU Patients Module 3 Anesthesia considerations, sleep apnea patients Morbid obesity, at risk for aspiration Difficult IV access Systemic + pulm HTN Cor pulmonale Airway obstruction + ventilatory arrest with anesthetic drugs  upper airway muscle activity inhibition of normal arousal patterns upper airway swelling from laryngoscopy, surgery, intubation Dexmedetomodine Anesthetic adjunct of choice to minimize opioid + sedative use
  • Pharmacologic Agents Used for the Sedative and Analgesic Management of ICU Patients Module 3 Vascular surgery patients Usually at risk for CAD, ischemia, HTN, tachycardia Dex attenuates periop stress response Dex attenuates  BP w AXC, especially thoracic aorta Dexmedetomidine RCT, n=41. Dex continued 48 hr postop HR  in dex gp at emergence 73 + 11 v. 83 + 20 bpm Better control of HR in dex gp Plasma NE levels  in dex gp
  • Pharmacologic Agents Used for the Sedative and Analgesic Management of ICU Patients Module 3 RCT, n= 25. Dex started at 0.5 to 0.7 ug/kg/hr 1 hr prior to end of surgery [vs.saline]. Double- blind Infusion adjusted according to need Dex continued in PACU PACU pain control with PCA Dexmedetomidine Morphine use  in dex gp (P < 0.03) Pain score better in dex gp: 1.8 vs 3.4 (P < 0.01) % time pain free in PACU  in dex gp: 44% vs 0 (P < 0.002) Better control of HR in dex gp
  • Pharmacologic Agents Used for the Sedative and Analgesic Management of ICU Patients Module 3
  • Pharmacologic Agents Used for the Sedative and Analgesic Management of ICU Patients Module 3
  • Pharmacologic Agents Used for the Sedative and Analgesic Management of ICU Patients Module 3 Lung Disease Often delays tracheal extubation RCT, n= 20. Dex started at end of surgery, 0.2 to 0.7 ug/kg/min, + continued 6 hr after extubation vs. controls (propofol) Ramsay > 3 before extub, 2 after extub Dexmedetomidine Faster time to extub: 7.8 + 4.6 h v. 16.5 + 11.8 h No difference in PaCO2 between gps 30 min after extub: 37.9 v. 34.9 mmHg
  • Pharmacologic Agents Used for the Sedative and Analgesic Management of ICU Patients Module 3 Thoracotomy + thoracoscopy patients COPD, pleural effusion, marginal pulmonary fct Thoracic epidural: mainly for thoracotomy Dex: excellent for thoracoscopy Dexmedetomidine Patients are arousable, but sedated Does not dec ventilatory drive Greatly dec need for opioids Alternative to thoracic epidural Continue in PACU/ ICU
  • Pharmacologic Agents Used for the Sedative and Analgesic Management of ICU Patients Module 3 Vascular surgery patients Usually at risk for CAD, ischemia, HTN, tachycardia Dex attenuates periop stress response Dex attenuates  BP w aortic cross clamp Dexmedetomidine RCT, n=41. Dex started 20 min before surgery + continued 48 hr after surgery, v. controls HR  in dex gp at emergence: 73 + 11 v. 83 + 20 bpm Better control of HR in dex gp Plasma NE levels  in dex gp
  • Pharmacologic Agents Used for the Sedative and Analgesic Management of ICU Patients Module 3 23 trials, n=3395.  mortality, all surgeries  ischemia, all surgeries  MI + mortality after vascular surgery  ischemia during cardiac surgery  BP during cardiac surgery (more hypotension) My Conclusions: Not class 1 evidence yet but trials look promising, especially vascular surgery
  • Pharmacologic Agents Used for the Sedative and Analgesic Management of ICU Patients Module 3 Neck + back surgery Dex causes minimal effect on SSEP monitoring Smooth emergence, especially cervical spine Easy to evalute neuro fct prior to + after extub Abdominal surgery Dexmedetomidine provides analgesia without respiratory depression Especially useful in elderly undergoing colon resections, TAH, + other stressful procedures
  • Pharmacologic Agents Used for the Sedative and Analgesic Management of ICU Patients Module 3
  • Pharmacologic Agents Used for the Sedative and Analgesic Management of ICU Patients Module 3 Transient hypertension: with rapid bolus Hypotension may occur, especially if hypovolemia  HR (attenuation of tachycardia): usually desirable  conc inhaled agents: BIS monitoring Potentiates benzodiazepines  narcotic use Continue infusion in PACU / ICU
  • Pharmacologic Agents Used for the Sedative and Analgesic Management of ICU Patients Module 3 The alpha-2 agonist effect of dexmedetomidine has been used to manage burn patients in several centers This agent can be used in both intubated and nonintubated burn patients The standard loading dose of dexmedetomidine is 0.4 to 0.7 mcg/kg Lower doses can be used for less severe burns and nonintubated patients and for outpatient burn care
  • Pharmacologic Agents Used for the Sedative and Analgesic Management of ICU Patients Module 3 Many trauma patients are intoxicated males with uncleared spines. They are at risk for serious injury if they move or thrash. Typically, an alcohol withdrawal regimen uses benzodiazepines, but patients often require intubation and ventilation due to extreme agitation The use of dex allows patients to breathe spontaneously, controls their heart rate and blood pressure, prevents the autonomic effects of withdrawal, and provides adequate sedation
  • Pharmacologic Agents Used for the Sedative and Analgesic Management of ICU Patients Module 3 Overall goal of anesthesia is to establish + maintain adequate drug concentration at effector site to produce desired effect Dex can help optimize anesthesia via: Sedation/hypnosis, analgesia +  sympathetic activity Attenuation of stress response with  HR Smooth emergence + tracheal extubation Unique mechanism of action on natural sleep pathway permits patients to be well rested yet easily aroused Pain control w/o respiratory depression Adjunct agent of choice for many surgeries
  • Training ppt of xamdex

    1. 1. Dexmedetomidine in ICU Sedation Dr Sunita Goel Consultant anesthesiologist Saifee Hospital Mumbai, India
    2. 2. ICU: A stressful environment
    3. 3. Common Causes of Anxiety in the ICU <ul><li>An innate sense of fear for the life-threatening illness </li></ul><ul><li>A sense of helplessness and loss of control </li></ul><ul><li>The inability to communicate effectively </li></ul><ul><li>Therapeutic interventions </li></ul><ul><li>Disorientation & memory loss </li></ul><ul><li>Sleep deprivation and </li></ul><ul><li>ICU surroundings- </li></ul><ul><ul><li>noise, light, alarms and </li></ul></ul><ul><ul><li>frequent movement of healthcare personnel </li></ul></ul>Anxiety adds to the stress caused by the disease & therapy Semin Respir Crit Care Med. 2001;22(2):165-74
    4. 4. Anxiety & Stress Response <ul><li>Heightened stress induces a Neuroendocrine response </li></ul><ul><ul><li> sympathetic activity </li></ul></ul><ul><ul><li> Adrenaline, ACTH, GH, Aldosterone, </li></ul></ul><ul><ul><li>Release of cytokines  inflammatory response </li></ul></ul><ul><li>Stress Response contributes to </li></ul><ul><ul><li>Hyperglycemia, </li></ul></ul><ul><ul><li>Increased metabolism & </li></ul></ul><ul><ul><li>Increased oxygen demand </li></ul></ul><ul><li>Stress leads to physical and psychological exhaustion interfering with patients’ ability to recover </li></ul>J Anesth Clin Pharmacology 2007; 23(3): 241-247
    5. 5. Role Sedation in ICU <ul><li>Reduce anxiety & agitation </li></ul><ul><li>Facilitate mechanical ventilation. </li></ul><ul><li>Induce sleep when required </li></ul><ul><li>Avoid or reduce delirium </li></ul><ul><li>Induce amnesia and prevent post-ICU psychosis </li></ul><ul><li>Facilitate patient’s communication </li></ul><ul><li>Attenuate the harmful adrenergic response </li></ul><ul><li>To improve patient comfort and safety </li></ul>
    6. 6. The Sedation Continuum Continuum of Depth of Sedation emedicine.medscape.com Minimal Sedation (anxiolysis) Moderate Sedation/ Analgesia Deep Sedation/ Analgesia General Anesthesia Responsiveness Normal response to speech Purposeful response to speech or touch Purposeful response to repeated or painful stimulation No response, even to pain Airway Unaffected Remains open May need help to maintain airway Often needs help to maintain airway Spontaneous Breathing Unaffected Adequate May not be adequate Often require ventilatory support Heart Function Unaffected Usually maintained Usually maintained May be impaired
    7. 7.
    8. 8. Target of Interventions (sedation) <ul><li>Optimum sedation </li></ul><ul><ul><li>neither under-sedation nor over-sedation </li></ul></ul><ul><li>Free from anxiety & pain </li></ul><ul><li>Calm & cooperative </li></ul>1. Crit Care . 2000;4(suppl 1):S110, 2. NEJM 2000;342:1471-1477, 3. Crit Care Med. 2005;33:1266-1271.
    9. 9. Cooperative Sedation <ul><li>Patient easily transitions from sleep to wakefulness and task performance when aroused 1 </li></ul><ul><ul><li>And able to resume rest when not stimulated 1 </li></ul></ul><ul><li>Allows for accurate Neuropsychological evaluation 1 </li></ul><ul><li>Facilitates patient’s participation in therapeutic maneuvers and in care decisions 2 </li></ul><ul><li>Most useful during procedures in which patient’s communication must be maintained1 </li></ul>http://health. enotes .com/medicine-encyclopedia/sedation 1-Bekker AY, et al. Neurosurgery. 2005;57(1 Suppl 1):1-10. 2-Burns AM, et al. Drugs . 1992;43:507-515.
    10. 10. Characteristics of an Ideal Sedative <ul><li>Rapid onset of action </li></ul><ul><li>Rapid recovery after discontinuation </li></ul><ul><li>Adequate sedation & predictable dose response </li></ul><ul><li>Easy to administer & titrate </li></ul><ul><li>Promotes natural sleep </li></ul><ul><li>Not altered by renal or hepatic disease </li></ul>1. JAMA. 2000;283:1451-1459. 2. Crit Care Med . 2002;30:119-141. 3. Pharmacotherapy. 2006;26:798-805.
    11. 11. <ul><li>Fewer adverse effects </li></ul><ul><li>No drug accumulation </li></ul><ul><li>Minimal adverse interaction with other drugs </li></ul><ul><li>Wide therapeutic index </li></ul><ul><li>Maintain Hemodynamic and Respiratory stability </li></ul><ul><li>Achieve sedation, while maintaining Arousability and Cooperation </li></ul>Characteristics of an Ideal Sedative.. 1. Anesthesiology . 2003;98:428-436, 2. Drugs 2000 Feb; 59 (2): 263-268, 3. Use of Sedative Medications in the Intensive Care Unit. www.medscape.com
    12. 12. Current Sedative & Analgesics in Critical Care
    13. 13. Limitations of sedative agents GABA related agents cause clouding of consciousness
    14. 14.
    15. 15. α 2 -Adrenergic Receptors & Effects <ul><li>α 2A & α 2C adrenergic receptors are widely present in CNS </li></ul><ul><li>α 2B receptors in the vascular smooth muscles </li></ul><ul><li>Most of the clinical effects are due to inhibitory α 2 receptors ( α 2A & α 2C ) </li></ul>BUMC PROCEEDINGS 2001;14:13–21. Goodman & Gilman. .The pharmacological Basis of therapeutics. 11th edition . Dexmedetomidine, US FDA approved prescribing information. Receptor Type Stimulation causes Alpha 2 A - Presynaptic Sedation & Analgesia Hypotension & Bradycardia Alpha 2 B - Postsynaptic Transient hypertension due to vasoconstriction Reflex bradycardia Alpha 2 C Modulates dopamine transmission in brain
    16. 16. Dexmedetomidine: Alpha-Adrenoceptor Selectivity <ul><li>Norepinephrine </li></ul><ul><li>Epinephrine </li></ul><ul><li>Dopamine </li></ul><ul><li>Tizanidine </li></ul><ul><li>Clonidine </li></ul><ul><li>Mivazerol </li></ul><ul><li>Guanfacine </li></ul><ul><li>Guanabenz </li></ul><ul><li>Medetomidine </li></ul><ul><li>Dexmedetomidine </li></ul>Alpha 2 Alpha 1 DXMD is 8 times more selective than Clonidine α2:α1 = 1600:1 vs 200:1 Alpha-Adrenoceptor Agonists
    17. 17. DXMD vs Clonidine <ul><li>Clonidine </li></ul><ul><li>Selectivity: α2:α1=200:1 </li></ul><ul><li>Primarily Anti-HTN </li></ul><ul><li>Analgesic adjunct </li></ul><ul><li>t 1/2 : 8 hr </li></ul><ul><li>Delayed recovery </li></ul><ul><li>Dexmedetomidine </li></ul><ul><li>Selectivity: α2:α1=1600:1 </li></ul><ul><li>Primarily Sedative </li></ul><ul><li>Analgesic adjunct </li></ul><ul><li>t 1/2 : 2 hr </li></ul><ul><li>Early recovery </li></ul>
    18. 18. DXMD Dexmedetomidine Hydrochloride
    19. 19. DXMD: Mechanism of Sedation <ul><li>Most selective α -2 Adrenergic Agonist- 8 times more selective than Clonidine ( α2:α1 = 1600:1 vs 200:1) </li></ul><ul><li>Produce sedation and analgesia by activation of the α 2 receptors in the brain and spinal cord </li></ul>
    20. 20. α 2 -Adrenergic Receptors & Effects <ul><li>α 2A & α 2C adrenergic receptors are widely present in CNS </li></ul><ul><li>Transient hypertension due vasoconstriction ( α 2B receptors) may occur at a high dose or rapid rate of infusion. </li></ul>BUMC PROCEEDINGS 2001;14:13–21. Goodman & Gilman. .The pharmacological Basis of therapeutics. 11th edition . Dexmedetomidine, US FDA approved prescribing information. Receptor Type Stimulation causes Alpha 2 A - Inhibitory Sedation & Analgesia Hypotension & Bradycardia Alpha 2 B - Excitatory Transient hypertension due to vasoconstriction Reflex bradycardia Alpha 2 C - Inhibitory Modulates dopamine transmission in brain
    21. 21. BUMC PROCEEDINGS 2001;14:13–21 DXMD: Clinical Effects
    22. 22. DXMD: Clinical Characteristics <ul><li>Cooperative and Dose dependant sedation 1 </li></ul><ul><li>Mimics Natural Sleep 1 </li></ul><ul><li>Anxiolysis & Analgesia 2,3 </li></ul><ul><li>Potentiates effects of opioids, sedatives, and anesthetics </li></ul><ul><li>Controls hyperadrenergic response to stress 1-3 </li></ul><ul><li>Reduces shivering 3 </li></ul><ul><li>No respiratory depression </li></ul><ul><li>Predictable cardiovascular response </li></ul>1. Drugs of the Future . 1993;18:49-56. 2. Anesthesiology . 2000;93:1345-1349. 3. Clin Pharmacokinet . 1997;33:426-453
    23. 23. Pharmacokinetic Profile <ul><li>Route: Intravenous infusion (recommended route) </li></ul><ul><ul><li>Loading: 1mcg/kg over 10 min </li></ul></ul><ul><ul><li>Maintenance: 0.2-0.7 mcg/kg/hr </li></ul></ul><ul><li>Half Life: </li></ul><ul><ul><li>Short distribution half-life (6 min): Rapid onset of sedation </li></ul></ul><ul><ul><li>Short elimination half-life (2 hr): Facilitates clearance </li></ul></ul><ul><li>Protein binding: 94% </li></ul><ul><li>Metabolized in liver almost completely </li></ul><ul><li>Elimination: Renal excretion </li></ul>Drugs 2000 Feb; 59(2): 263-268 Critical Care Nurse 2010 Feb;30(1):29-39
    24. 24. DXMD: Concentration Dependent Sedation OAA/S: Composite Observer Assessment of Alertness/ Sedation score of 9 to 20 (20- maximum alertness). VAS: A visual analog scale with end points of very alert (0) to very sedated (100). §: Significant change in variable during dexmedetomidine infusions. Adapted from Ebert et al. Anesthesiology. August 2000; 93(2):382-394 0.9ng/ml with 1mcg/kg
    25. 25. Arousability from Sedation During DXMD Infusion <ul><li>DXMD 0.2 or 0.6 mcg/kg/hr vs Placebo </li></ul><ul><li>Monitored by BIS score </li></ul><ul><ul><li>before & during cognitive and cold pressor tests </li></ul></ul><ul><li>Patients receiving DXMD could be completely aroused by a mild stimulus </li></ul>Hall JE, et al. Anesth Analg . 2000;90:699-705.
    26. 26. Dexmedetomidine produces Stage 2 NREM sleep <ul><li>Dexmedetomidine produces a state closely resembling physiological Stage 2 Non Rapid Eye Movement sleep </li></ul>Acta Anaesthesiol Scand 2008; 52: 289–294
    27. 27. DXMD produces st-2 of NREM sleep by removing the inhibitory impulse from LC inhibition uninhibited Anesthesiology 2003; 98:428–36
    28. 28. DXMD Spares Cognitive Function <ul><li>DXMD significantly improved ACE score vs Propofol </li></ul><ul><li>(Difference in ACE score 19.2; p<0.001) </li></ul><ul><li>Higher ACE scores with DXMD shows the intellect-sparing yet calming effect of this drug. </li></ul><ul><li>With DXMD, ICU patients may be offered sedation without necessarily compromising arousal or cognition </li></ul>Intensive Care Med. 2010 Apr 8. [Epub ahead of print] ACE: Adapted Cognitive Examination <ul><ul><li>( -12.4, p < 0.001) </li></ul></ul>(+6.8, p<0.018)
    29. 29. DXMD: Respiratory Stability Ebert et al. Anesthesiology. August 2000; 93(2):382-394 † † † Respiratory Rate breaths/min Plasma Dexmedetomidine (ng/mL) Data are mean ± SEM. * Target DXMD conc. in ng/mL † P< 0.05 compared with baseline values. 0.9ng/ml with 1mcg/kg mm Hg PaO 2 mm Hg PaCO 2 † † †
    30. 30. DXMD: Predictable Hemodynamic Responce Ebert et al. Anesthesiology. August 2000; 93(2):382-394 Plasma Dexmedetomidine (ng/mL) 0.9ng/ml with 1mcg/kg
    31. 31. Bradycardia & Hypotension Predictable cardiovascular Effects <ul><li>Within an hour of commencing an infusion of 1.0 μg/kg/hr </li></ul><ul><ul><li>10% drop in systolic blood pressure and </li></ul></ul><ul><ul><li>10-15% drop in heart rate are expected. </li></ul></ul><ul><li>May be exaggerated in patients </li></ul><ul><ul><li>Who receive a loading dose, or </li></ul></ul><ul><ul><li>Who are hypovolaemic or </li></ul></ul><ul><ul><li>Who ARE receiving other vasodilators. </li></ul></ul><ul><li>Management </li></ul><ul><ul><li>Restore intravascular volume- 10 ml/kg fluid bolus. </li></ul></ul><ul><ul><li>Vasopresors for hypotension </li></ul></ul><ul><ul><li>Atropine/ Gycopyrolate for bradycardia </li></ul></ul>Crit Care & Shock 2010. Vol 13, No.2:40-50
    32. 32. Clinical Trials in ICU Sedation
    33. 33. SEDCOM Trial: DXMD vs Midazolam <ul><li>A double-blind, RCT in 68 centers in 5 countries </li></ul><ul><li>375 medical/surgical ICU patients with expected MV for >24 hours </li></ul><ul><li>DXMD 0.2- 1.4 µg/kg/hr (n=244) or Midazolam 0.02-0.1mg/kg/hr (n=122) titrated to achieve light sedation (RASS −2 to 1) until extubation or 30 days. </li></ul><ul><li>Similar % of time within the target RASS range (77.3% vs 75.1%) </li></ul><ul><li>Higher nurse-to-patient cooperation </li></ul><ul><li>Fewer infections in DXMD group </li></ul>CT in ICU sedation- 1 JAMA 2009;301(5):489-499 SEDCOM (Safety and Efficacy of Dexmedetomidine COmpared With Midazolam).
    34. 34. SEDCOM Trial: DXMD vs Midazolam CT in ICU sedation- 1 P= 0 .01 SEDCOM (Safety and Efficacy of Dexmedetomidine COmpared With Midazolam). <ul><li>Early Extubation: Median time reduced by 1.9 days </li></ul><ul><ul><li>3.7days with DXMD vs 5.6 days with Midazolam ( P= 0 .01 ) </li></ul></ul><ul><li>Shorter LOS in ICU (1.3 days) </li></ul>JAMA 2009;301(5):489-499 <ul><li>Bradycardia 42%, only 4.9% needed intervention </li></ul><ul><li>Significantly less Tachycardia & HTN </li></ul>3.7 days 5.6 days 0 2 4 6 Time to extubation in days Dexmedetomidine-treated patients spend less time on ventilator Dexmedetomidine Midazolam
    35. 35. DEXCOM study: DXMD vs Morphine-based regimen after Cardiac Surgery <ul><li>306 patients , at least 60 yr old; treated with DXMD or Morphine with open-label Propofol; Target sedation: MAAS of 2–4. </li></ul><ul><li>Results: </li></ul><ul><li>Sedation profile was similar in both groups </li></ul><ul><li>Median DXMD dose used 0.49 mcg/kg/hr </li></ul><ul><li>DXMD promoted early extubation (P = 0.040), </li></ul><ul><li>DXMD-treated patients </li></ul><ul><ul><li>Required less propofol (total dose) </li></ul></ul><ul><ul><li>Less systolic hypotension (23% vs 38.1%, P= 0.006), </li></ul></ul><ul><ul><li>Required less norepinephrine ( P < 0.001) </li></ul></ul><ul><ul><li>More bradycardia than morphine treatment . </li></ul></ul><ul><li>Conclusion: </li></ul><ul><li>DXMD produced effective analgesia/sedation, less hypotension, less vasopressor requirement, vs morphine regimen, and reduced the duration of delirium. </li></ul>DEXCOM study: Anesthesiology 2009; 111:1075–84 DEXCOM: DEXmedetomidine COmpared to Morphine
    36. 36. Pediatric Patients in ICU: DXMD Reduces Opioid & BDZ requirement <ul><li>Critically ill infants and children (n=29), av age 6 yr </li></ul><ul><li>DXMD (0.1-1.5 µg/kg/hour) for 110 hours </li></ul><ul><ul><li>R ange: 32-378 hr </li></ul></ul><ul><ul><li>Median = 76 hr </li></ul></ul><ul><li>Conclusion : </li></ul><ul><li>Prolonged DXMD infusion reduced opiod & BDZ requirement </li></ul>Indian Pediatrics 2009 April 1 CT- 2 54% 45% 0% 10% 20% 30% 40% 50% 60% % of Patients Discontinued Opioids Discontinued BDZs Patients able to discontinue Opioid & BDZ after DXMD administration
    37. 37. Noninvasive Ventilation (NIV) in ICU <ul><li>10 patients in whom NIV was difficult because of agitation </li></ul><ul><li>DXMD maintains adequate sedation level in NIV </li></ul><ul><ul><li>RSS score at 2.94 ± 0.94; RASS scores -1.23 ± 1.30. </li></ul></ul><ul><li>All patients were successfully weaned from NIV , and the respiratory state was not worsened. </li></ul>Anesth Analg 2008;107:167–70 NIV may fail if patient develops claustrophobia, agitation or intolerance to mask or nasal ventilation
    38. 38. Routine Care in ICU <ul><li>Top 3 reasons for prescribing Dexmedetomidine </li></ul><ul><ul><li>to assist in weaning, </li></ul></ul><ul><ul><li>reduce the use of other narcotic or sedative drugs and </li></ul></ul><ul><ul><li>maintain the patient alertness. </li></ul></ul><ul><li>136 patients from 10 ICUs in USA </li></ul><ul><li>Result: </li></ul><ul><ul><li>34 % of the patient received DXMD for > 24 hours. </li></ul></ul><ul><ul><li>DXMD maintained its expected efficacy & safety profile </li></ul></ul><ul><ul><li>Adverse Drug Reactions rates are similar to those of other published report </li></ul></ul>Ann Pharmacotherpy 2004; 38: 1130-5. CT- 4
    39. 39. Introducing DXMD in General ICU for Primary Sedation <ul><li>42 medical & surgical patients on MV in General ICU </li></ul><ul><li>Dissatisfaction associated with oversedation with current sedatives </li></ul><ul><li>DXMD use: Before vs After </li></ul><ul><li>272 fewer total ICU days, 19% decrease ( P = .05) </li></ul><ul><li>Mean length of stay : 2.34 vs 2.31 days (1.5% reduction; P = .05) </li></ul>Crit Care Nurse. 2010;30: 29-38
    40. 40. Sedatives & Delirium <ul><li>Improper sedation increases the risk of delirium </li></ul><ul><ul><li>BDZ use increases the risk </li></ul></ul><ul><li>Goal: To reduce brain dysfunction (delirium and coma) while providing efficacious sedation. </li></ul><ul><li>DXMD: Reduce the risk of delirium, facilitates extubation in agitated delirious patients </li></ul><ul><li>MENDS Trial: M aximizing E fficacy of Targeted Sedation and Reducing N eurological D ysfunction </li></ul>MENDS trial. JAMA 2007;298(22):2644-2653. Anesthesiology . 2006;104(1):21-26. J Trauma. 2008 Jul;65(1):34-41.
    41. 41. MENDS trial: DXMD vs. Lorazepam Maximizing Efficacy, Reducing Brain Dysfunction CT- 15 <ul><li>106 medical and surgical ICU patients requiring mechanical ventilation >24 hrs </li></ul><ul><li>Sedated with DXMD or Lorazepam for up to 120 hours; Fentanyl for analgesia </li></ul>MENDS trial. JAMA 2007;298(22):2644-2653 P = 0.01 P < 0.001 7 3 0 1 2 3 4 5 6 7 No of days alive without delirium or coma DXMD increased the no of delirium- or coma-free days 63 92 0 20 40 60 80 100 Prevalence of Coma DXMD lowers the prevalence of coma DXMD + F Lorazepam + F
    42. 42. MENDS trial: DXMD vs. Lorazepam Sedation goals better achieved with DXMD <ul><li>Sedation goals better achieved with DXMD </li></ul><ul><li>Patients spent more time within 1 RASS point of their sedation goal </li></ul><ul><ul><li>(median % of days, 80% vs 67%; P =.04 ). </li></ul></ul><ul><li>In any given day, between 5% and 15% more DXMD-treated patients were at target sedation level compared with lorazepam-treated patients. </li></ul>MENDS trial. JAMA 2007;298(22):2644-2653 CT- 15 Percentage of Patients by Study Day Who Were Within 1 Point of the RASS Sedation Goal While Receiving Study Drug
    43. 43. <ul><li>More ventilator free days : 22 vs 18 days </li></ul><ul><li>Less 28-day mortality in the DXMD gr : 17% vs 27% </li></ul><ul><li>More time to death within 12 months : 363 vs 188 days in the lorazepam group </li></ul><ul><li>More patients (42% vs 31%; P =.61) were able to complete post-ICU neuropsychological testing </li></ul><ul><ul><li>with similar scores in the tests evaluating global cognitive, motor speed, and attention functions. </li></ul></ul><ul><li>Cost of care was similar between groups . </li></ul>MENDS trial: DXMD vs. Lorazepam Maximizing Efficacy, Reducing Brain Dysfunction MENDS trial. JAMA 2007;298(22):2644-2653
    44. 44. DXMD vs Morphine & Propofol Reduction of Delirium after Cardiac Surgery <ul><li>Results: Less i ncidence of delirium with DXMD </li></ul><ul><li>DXMD- 3%, Propofol- 50%, and Midazolam- 50% (PP) </li></ul><ul><li>DXMD- 10%, Propofol- 44%, and Midazolam- 44% (ITT ) </li></ul><ul><li>Absolute risk reduction- 47%, NNT 2.1 </li></ul>Psychosomatics 2009; 50:206 –217 <ul><li>Post-op sedation after cardiac surgery </li></ul><ul><li>Open-label, randomized study, N=118; </li></ul><ul><li>DXMD-40, Propofol- 38, Midazolam-40 </li></ul>
    45. 45. DXMD vs Morphine & Propofol Delirium after Cardiac Surgery <ul><li>Postoperative sedation with DXMD was associated with </li></ul><ul><ul><li>significant lower rates of postoperative delirium & </li></ul></ul><ul><ul><li>significant lower care costs </li></ul></ul>Psychosomatics 2009; 50:206 –217
    46. 46. Sedation during Weaning/Extubation <ul><li>Anxiety, fear and agitation are amongst the most common non-pulmonary causes of failure to liberate from mechanical ventilation. </li></ul><ul><li>Ventilated patients receiving opioids and/or BDZs can NOT be easily weaned off ventilation, because </li></ul><ul><ul><li>If these drugs are stopped prior to weaning, the patients are at high risk of developing agitation. </li></ul></ul><ul><ul><li>If these drugs are NOT stopped, the patient may go to respiratory failure after weaning-- reventilation. </li></ul></ul><ul><li>This is often associated with an increased intubation time and length of stay in the ICU and may cause long-term morbidity. </li></ul>
    47. 47. DXMD Facilitates weaning after failure of conventional therapy. <ul><li>28 ventilated adult patients in the ICU (30 episodes) on opioids / sedatives for >24 hours, </li></ul><ul><ul><li>who developed agitation and/or delirium upon weaning from sedation and failed to achieve successful extubation </li></ul></ul><ul><li>DXMD achieved rapid resolution of agitation </li></ul><ul><ul><li>Weaning was successful in 73.3% cases </li></ul></ul><ul><li>DXMD facilitated ventilatory weaning after failure of conventional therapy. </li></ul>Anaesth Intensive Care. 2010 Jan;38(1):82-90.
    48. 48. Mechanically Ventilated Patients with Delirium: vs. Haloperidol <ul><li>Patients on mechanical ventilation </li></ul><ul><li>Extubation was not possible solely because of agitated delirium </li></ul><ul><li>Treatment : </li></ul><ul><li>Haloperidol or DXMD </li></ul>P=0.004 Critical Care 2009 vol 13 No 3 CT- 16 n=20 <ul><li>Results: DXMD significantly reduced Length of ICU stay </li></ul><ul><ul><li>(1.5 vs.6.5 days, P=0.004 ). </li></ul></ul>
    49. 49. DXMD: The Unique Sedative during Weaning/Extubation <ul><li>Suggestion supported by clinical Evidence: </li></ul><ul><li>Add DXMD- Reduce these drugs- Extubate – Stop DXMD </li></ul><ul><li>This facilitates extubation and it is probably much less expensive than spending another day on ventilation </li></ul>
    50. 50. Transition from other sedatives Crit Care & Shock (2010) 13:40-50 New Dosing Protocol
    51. 51. Weaning: Switching to DXMD <ul><li>DXMD infusion 2 hours before stopping other sedative </li></ul><ul><ul><li>0.4 μg/kg/hr (without loading dose) for 2 hours </li></ul></ul><ul><ul><li>Titrated by 0.2 μg/kg/hr every 30 minutes to achieve light sedation </li></ul></ul><ul><li>Concurrent sedative/narcotic can be weaned 2 hr after initiating DXMD infusion . </li></ul><ul><li>Rescue sedation, if episodes of agitation </li></ul><ul><ul><li>Midazolam 1 mg and/or Propofol 25-30 mg </li></ul></ul><ul><li>Additional analgesia, if required </li></ul><ul><ul><li>Morphine 1-2 mg or Fentanyl 10-20 μg </li></ul></ul>
    52. 52. DXMD vs. Other Sedative/Analgesics Comparison of Clinical Effects Crit Care Nurse. 2010;30: 29-38   BDZ Propofol Opiods Haloperidol DXMD Sedation      Anxiolytic       Analgesic       Maintain arousability during sedation & Facilitate weaning               No respiratory depression         Control Delirium        
    53. 53. DXMD vs. Other Sedative/Analgesics Comparison of Adverse Effects   BDZ Propofol Opiods Haloperidol DXMD Prolonged weaning      Respiratory depression      Hypotension      Constipation        Deliriogenic      Tachycardia     Morphine   Bradycardia     Fentanyl  
    54. 54. Potential role of DXMD for sedation in the Intensive Care Unit BUMC PROCEEDINGS 2001;14:13–21
    55. 55. DXMD: The Ideal Sedative in ICU Patients <ul><li>Unique sedative properties </li></ul><ul><ul><li>Maintains arousability during sedation & Facilitates weaning </li></ul></ul><ul><ul><li>Does not cause respiratory depression </li></ul></ul><ul><li>DXMD infusion can continue </li></ul><ul><ul><li>through mechanical ventilation, </li></ul></ul><ul><ul><li>during extubation and </li></ul></ul><ul><ul><li>in the postextubation period. </li></ul></ul><ul><li>Allows greater flexibility for the timing of extubation as well as allowing patients to be calm, comfortable and pain free during the process. </li></ul>Drugs 2000 Feb; 59 (2): 269-270
    56. 56. DXMD: Indications <ul><li>ICU sedation </li></ul><ul><ul><li>Intubated and mechanically ventilated patients in ICU * </li></ul></ul><ul><li>Procedural sedation </li></ul><ul><ul><li>Non-intubated patients prior to and/or during surgical and other procedure ** </li></ul></ul>Dexmedetomidine DCGI approval : *29.05.09 and ** 14.11.2009. http://cdsco.nic.in/Newdrugslisttilljuly2009.htm
    57. 57. DXMD: Off Label Use <ul><li>To control agitation in patients receiving noninvasive ventilatory support </li></ul><ul><li>As Anesthetic Adjuvant </li></ul><ul><ul><li>Adjunct to general & regional (IVRA) anesthesia </li></ul></ul><ul><ul><li>Supplement to regional block in patients undergoing carotid endarterectomy or during awake craniotomy </li></ul></ul><ul><li>To treat shivering </li></ul><ul><li>To minimize withdrawal phenomena in patients who have received long-term BDZ and Opioids during their hospitalization. </li></ul>Reference: Drugs Facts and Comparisons, 2009: p-1481
    58. 58. DXMD: Dosage and Administration <ul><li>A dose reduction should be considered for patients </li></ul><ul><ul><li>over 65 years of age </li></ul></ul><ul><ul><li>with hepatic or renal impairment </li></ul></ul>Loading: 0.5-1mcg/kg over 10 min Maintenance: 0.2-0.7 mcg/kg/hr ICU Sedation Initiation (Loading dose) <ul><li>1 mcg/kg over 10 minutes </li></ul>Maintenance <ul><li>0.2 to 0.7 mcg/kg/hr </li></ul>Procedural Sedation Loading dose <ul><li>1 mcg/kg over 10 minutes </li></ul><ul><li>0.5 mcg/kg over 10 minutes for less invasive procedures </li></ul>Maintenance <ul><li>Initiated at 0.6 mcg/kg/hr and titrated 0.2 to 1 mcg/kg/hr </li></ul><ul><li>For AFOI: 0.7 mcg/kg/hr until the ET tube is secured </li></ul>
    59. 59. DXMD: Dosage for ICU Sedation <ul><li>Loading dose: </li></ul><ul><ul><li>1 mcg/kg over 10 minutes </li></ul></ul><ul><ul><li>0.5 mcg/kg over 10 minutes* </li></ul></ul><ul><ul><li>Some protocols & studies omitted the LD </li></ul></ul><ul><li>Maintenance dose: </li></ul><ul><ul><li>0.2 to 0.7 mcg/kg/hr * </li></ul></ul><ul><ul><ul><li>Titrate to achieve the desired level of sedation </li></ul></ul></ul><ul><ul><li>Upto 1.4 mcg/kg/hr has been given </li></ul></ul><ul><li>A dose reduction should be considered for patients* </li></ul><ul><ul><li>over 65 years of age </li></ul></ul><ul><ul><li>with hepatic & renal impairment </li></ul></ul>
    60. 60. DXMD: Dosage and Administration <ul><li>Should be diluted to 50 ml with 0.9% NaCl & administered using a controlled infusion device. </li></ul><ul><li>Dosing should be individualized; Rate of the maintenance infusion should be titrated to desired clinical response and target level of sedation. </li></ul><ul><li>Continuous infusion for 24 hr. However, found to be effective and well tolerated during prolong use (upto a 30days) without rebound </li></ul><ul><li>Reduction in dosage of Dexdine or other concomitant anesthetics, sedatives, hypnotics or opioids during co-administration </li></ul>
    61. 61. Adverse Effects <ul><li>The most common adverse reactions are </li></ul><ul><ul><li>Hypotension </li></ul></ul><ul><ul><li>Bradycardia </li></ul></ul><ul><ul><li>Dry mouth </li></ul></ul><ul><li>Transient hypertension may be seen during a loading dose </li></ul>Drugs 2000;59:263–268.
    62. 62. New Dosing Protocol Dex=dexmedetomidine; Fent=fentanyl. Crit Care & Shock (2010) 13:40-50 Additional sedation and analgesia should be kept to a minimum guided by sedation targets and the adequacy of pain relief Sedation Advisory Board in Intensive Care, Prince of Wales Hospital, Australia
    63. 63. Transient Hypertension Predictable cardiovascular Effects <ul><li>May be seen during loading dose in some patients </li></ul><ul><li>Never give as a bolus: Mark the infusion device “ DO NOT BOLUS” </li></ul><ul><li>Alternative Strategy </li></ul><ul><li>Loading dose may be omitted or over longer period </li></ul><ul><li>Infusion should start at 0.4 μg/kg/hr for one hour then increased by 0.1 to 0.2 μg/kg/hr every 30 minutes as necessary </li></ul>Crit Care & Shock 2010. Vol 13, No.2:40-50
    64. 64. Transient Hypertension Predictable cardiovascular Effects <ul><li>May be seen during loading dose in some patients </li></ul><ul><li>Should never be given as a bolus </li></ul><ul><li>Mark the infusion device “DO NOT BOLUS” </li></ul><ul><li>Alternative Strategy </li></ul><ul><li>No Loading dose; Start i nfusion at 0.4 μg/kg/hr for 1 hour </li></ul><ul><ul><li>Peak effect in 45-60 minutes </li></ul></ul><ul><li>Then titrate by 0.1 to 0.2 μg/kg/hr every 30 minutes </li></ul>Crit Care & Shock 2010. Vol 13, No.2:40-50
    65. 65. DXMD: Patient Selection <ul><li>Anxious, Agitated and Apprehensive patients </li></ul><ul><li>High sympathetic activity </li></ul><ul><li>Compromised respiratory function (COPD) </li></ul><ul><li>Difficult airway and sleep apnea (obese patients) </li></ul><ul><li>History of delirium following previous operations </li></ul><ul><li>A critical need for cardiovascular stability, </li></ul><ul><ul><li>Avoidance of BP swings after thoracic aneurysm repair or aortic valve replacement </li></ul></ul><ul><li>Narcotic intolerance or history of abuse </li></ul>Crit Care & Shock (2010) 13:40-50. Crit Care Nurse. 2010;30: 29-38
    66. 66. DXMD: Avoid in patients with Refractory Haemodynamic Instability <ul><li>Low BP/ Shock not responding to vasopressors </li></ul><ul><ul><li>SBP < 90mmHg or a mean BP < 60 mmHg in spite of significant vasopressor support: </li></ul></ul><ul><ul><ul><li>(Vasopressin > 2 U/hr Noradrenaline or Adrenaline > 0.2 µg/kg/min or Dobutamine > 10 µg/kg/min) </li></ul></ul></ul><ul><li>HR<55 BPM, not induced by beta-blocker </li></ul><ul><li>Uncorrected Hypovolemia </li></ul><ul><li>Conduction defects: </li></ul><ul><ul><li>Severe ventricular dysfunction </li></ul></ul><ul><ul><li>High grade AV block in the absence of pace maker </li></ul></ul>Crit Care Nurse. 2010;30: 29-38. Crit Care & Shock (2010) 13:40-50
    67. 67. Sedation with DXMD: Advantages <ul><li>Sedation, anxiolysis, analgesia by single agent </li></ul><ul><li>Conscious sedation- cooperative & arousable </li></ul><ul><li>Quick onset of action & early recovery </li></ul><ul><li>Reduced anesthetic/analgesic requirements </li></ul><ul><li>Reduce delirium & length of stay </li></ul><ul><li>No respiratory depression </li></ul><ul><li>Decrease oxygen demand </li></ul><ul><li>Early weaning from ventilator; failed weaning cases </li></ul><ul><li>Blood pressure control without tachycardia </li></ul>
    68. 68. Conclusion <ul><li>Optimal sedation strategy in the critically ill should achieve targeted sedation, effective analgesia, and reduced risk of delirium and agitation , which is difficult with the conventional agents. </li></ul><ul><li>DXMD, as a single agent , produces conscious sedation, anxiolysis and analgesia, reduces anesthetic and analgesic requirements, reduces delirium and agitation, without respiratory depression and with predictable and desirable cardiovascular effects. </li></ul><ul><li>It is also useful for post operative analgesia and sedation in high risk and complex surgical patients , and during transition from other conventional sedatives . </li></ul><ul><li>Critically ill patients requiring ventilation for more than 24 hours and patients who experienced emergent agitation and or delirium have also been successfully managed with a dexmedetomidine regimen. </li></ul><ul><li>Addition of DXMD to the current standard of care would ensure improved clinical outcomes, reduced total hospital costs and ensure patient comfort </li></ul>
    69. 69. Clinical Uses of Dex in Anesthesia <ul><li>Bariatric surgery </li></ul><ul><li>Sleep apnea patients </li></ul><ul><li>Craniotomy: aneurysm, AVM [hypothermia] </li></ul><ul><li>Cervical spine surgery </li></ul><ul><li>Off-pump CABG </li></ul><ul><li>Vascular surgery </li></ul><ul><li>Thoracic surgery </li></ul><ul><li>Conventional CABG </li></ul><ul><li>Back surgery, evoked potentials </li></ul><ul><li>Head injury </li></ul><ul><li>Burn </li></ul><ul><li>Trauma </li></ul><ul><li>Alcohol withdrawal </li></ul><ul><li>Awake intubation </li></ul>
    70. 70. Sleep Apnea Patients <ul><li>Anesthesia considerations </li></ul><ul><li>Morbid obesity, at risk for aspiration </li></ul><ul><li>Difficult IV access </li></ul><ul><li>Systemic + pulm HTN, cor pulmonale </li></ul><ul><li>Postop airway obstruction + ventilatory arrest with anesthetic drugs </li></ul><ul><ul><li> upper airway muscle activity </li></ul></ul><ul><ul><li>inhibition of normal arousal patterns </li></ul></ul><ul><ul><li>upper airway swelling from laryngoscopy, surgery, intubation </li></ul></ul><ul><li>Dexmedetomodine </li></ul><ul><li>Anesthetic adjunct to minimize opioid + sedative use </li></ul>Ogan OU, Plevak DJ: Mayo Clinic; www.sleepapnea.org
    71. 71. Gastric Bypass Surgery Patients <ul><li>Morbidly obese patients </li></ul><ul><li>Prone to hypoxemia </li></ul><ul><li>Sleep apnea is common </li></ul><ul><li>Respiratory depression w opioids </li></ul><ul><li>Dexmedetomidine, 0.1 to 0.7 ug/kg/hr, prospectively studied in 32 pts </li></ul><ul><li> opioid use in dex group </li></ul><ul><li>1 pt in control gp needed reintubation </li></ul><ul><li>Dex pts more likely to be normotensive w  HR </li></ul>Craig MG et al: IARS abstract, 2002. Baylor
    72. 72. Dex Improves Postop Pain Mgt after Bariatric Surgery <ul><li>RCT, n= 25. Dex started at 0.5 to 0.7 ug/kg/hr 1 hr prior to end of surgery [vs.saline]. Double- blind </li></ul><ul><li>Infusion adjusted according to need </li></ul><ul><li>Dex continued in PACU </li></ul><ul><li>PACU pain control with PCA </li></ul><ul><li>Dexmedetomidine </li></ul><ul><li>Morphine use  in dex gp (P < 0.03) </li></ul><ul><li>Pain score better in dex gp: 1.8 vs 3.4 (P < 0.01) </li></ul><ul><li>% time pain free in PACU  in dex gp: </li></ul><ul><ul><li>44% vs 0 (P < 0.002) </li></ul></ul><ul><li>Better control of HR in dex gp </li></ul>Ramsay MA, et al: Anesthesiology, 2002: A-910 and A-165. Baylor
    73. 73. Craniotomy for Aneurysm / AVM <ul><li>Anesthesia considerations </li></ul><ul><li>Smooth induction + emergence </li></ul><ul><li>Prevent rupture </li></ul><ul><li>Avoid cerebral ischemia </li></ul><ul><li>Hypothermia (33 o C)  CMRO 2 , CBF, CBV, CSF, ICP </li></ul><ul><li>Dexmedetomodine </li></ul><ul><li> sympathetic stimulation </li></ul><ul><li> or no change in ICP </li></ul><ul><li> shivering w/o resp depression </li></ul><ul><li>Preserved cognitive fct </li></ul><ul><ul><li>reliable serial neuro exams </li></ul></ul>Doufas AG et al: Stroke 2003;34. Louisville, KY
    74. 74. Coronary Artery Surgery Patients <ul><li>Herr study, n=300: Dex vs. controls [propofol] </li></ul><ul><li>RCT, dex started at sternal closure, 0.4 ug/kg/hr after loading dose, and 0.2 to 0.7 ug/kg/hr for 6- 24 hrs after extubation </li></ul><ul><li>Ramsay > 3 before extub, Ramsay 2 after extub </li></ul><ul><li>Dexmedetomidine </li></ul><ul><li>Faster time to extub in dex gp </li></ul><ul><ul><li>by 1 hr </li></ul></ul><ul><li>94% did not require propofol </li></ul><ul><li>70% did not require morphine </li></ul><ul><ul><li>(vs. 34% controls) </li></ul></ul><ul><li>Dex pts had less Afib (7 vs 12 pts) </li></ul>Herr DL: Crit Care Med 2000;28:M248. Washington Hospital
    75. 75. CABG and Lung Disease <ul><li>Lung Disease </li></ul><ul><li>Often delays tracheal extubation </li></ul><ul><li>RCT, n= 20. Dex started at end of surgery, 0.2 to 0.7 ug/kg/hr, + continued 6 hr after extubation vs. controls (propofol) </li></ul><ul><li>Ramsay > 3 before extub, Ramsay 2 after extub </li></ul><ul><li>Dexmedetomidine </li></ul><ul><li>Faster time to extub: </li></ul><ul><ul><li>7.8 + 4.6 h v. 16.5 + 11.8 h </li></ul></ul><ul><li>No difference in PaCO2 between gps 30 min after extub: 37.9 v. 34.9 mmHg </li></ul>Sumping ST: CCM 2000;28:M249. Duke
    76. 76. Thoracotomy + Thoracoscopy <ul><li>Thoracotomy + thoracoscopy patients </li></ul><ul><li>COPD, pleural effusion, marginal pulmonary fct </li></ul><ul><li> pCO 2 +  pO 2 with opioids for analgesia </li></ul><ul><li>Thoracic epidural: mainly for thoracotomy </li></ul><ul><li>Dex: mainly for thoracoscopy </li></ul><ul><li>Dexmedetomidine </li></ul><ul><li>Patients are arousable, but sedated </li></ul><ul><li>Does not  ventilatory drive </li></ul><ul><li>Greatly  need for opioids </li></ul><ul><li>Alternative to thoracic epidural </li></ul><ul><li>Continue after extubation </li></ul>
    77. 77. Vascular Surgery <ul><li>Vascular surgery patients </li></ul><ul><li>Usually at risk for CAD, ischemia, HTN, tachycardia </li></ul><ul><li>Dex attenuates periop stress response </li></ul><ul><li>Dex attenuates  BP w AXC, especially thoracic aorta </li></ul><ul><li>Dexmedetomidine </li></ul><ul><li>RCT, n=41. Dex continued 48 hr postop </li></ul><ul><li>HR  in dex gp at emergence </li></ul><ul><ul><li>73 + 11 v. 83 + 20 bpm </li></ul></ul><ul><li>Better control of HR in dex gp </li></ul><ul><li>Plasma NE levels  in dex gp </li></ul>Talke et al: Anesth Analg 2000;90:834. Multicenter
    78. 78. Meta- Analysis of Alpha-2 Agonists <ul><li>23 trials, n=3395. </li></ul><ul><li>All surgeries:  mortality + ischemia </li></ul><ul><li>Vascular:  MI + mortality </li></ul><ul><li>Cardiac:  ischemia </li></ul><ul><li>Cardiac:  BP (more hypotension) </li></ul><ul><li>Conclusions: </li></ul><ul><li>Not class 1 evidence yet, but trials look promising </li></ul><ul><ul><li>Especially vascular surgery </li></ul></ul>Wijeysundera, Am J Med 2003;114:742. Univ of Toronto
    79. 79. Other Surgical Procedures <ul><ul><li>Neck + back surgery </li></ul></ul><ul><ul><ul><li>Dex causes minimal effect on SSEP monitoring </li></ul></ul></ul><ul><ul><ul><li>Smooth emergence, especially cervical spine </li></ul></ul></ul><ul><ul><ul><li>Easy to evalute neuro fct prior to + after extub </li></ul></ul></ul><ul><ul><li>Abdominal surgery </li></ul></ul><ul><ul><ul><li>Dexmedetomidine provides analgesia without respiratory depression </li></ul></ul></ul><ul><ul><ul><li>Especially useful in elderly undergoing colon resections, TAH, + other stressful procedures </li></ul></ul></ul>
    80. 80. Perioperative Dex Infusion Protocol Example: 70 kg patient. Assess BP, HR, volume status 2 mL Dex in 48 mL 0.9% saline= 200 ug/50 mL, or 4 ug/ml Hypovolemic Start at 40 mL/hr Stop load if  HR Usual load: 25 to 35 ug or 6 to 9 mL over 10-15 min Monitor BP/HR throughout If bradycardia,  infusion Maintenance: 0.2 to 0.7 ug/kg/hr [4 to 12 mL/hr] Volume preload 500 to 1000 cc LR Normovolemic Dex=dexmedetomidine.
    81. 81. Considerations With Anesthesia Use of Dexmedetomidine <ul><li>Dilute in 0.9% saline: 4 mcg/mL </li></ul><ul><li>Requires infusion pump: mcg/kg/h </li></ul><ul><li>Transient HTN: with rapid bolus </li></ul><ul><li>Hypotension may occur, especially if hypovolemia </li></ul><ul><li> HR (attenuation of tachycardia): usually desirable </li></ul><ul><li> conc of inhaled agents: BIS monitoring </li></ul><ul><li>Continue infusion after extubation for 30 min [PACU] </li></ul><ul><li>L + D: not studied </li></ul><ul><li>Pediatrics: abstracts + case reports [Lerman, Toronto] </li></ul><ul><li>Geriatrics: more hypotension + bradycardia:  dose </li></ul>
    82. 82. Use of Dexmedetomidine in the Burn Unit <ul><li> 2 agonist effect assists in the management of burn patients; blunts catecholamine surge </li></ul><ul><li>Use in intubated and non-intubated burn patients </li></ul><ul><li>Administer as a standard load once patient is normovolemic (range: 0.4 to 0.7 mcg/kg/hr) </li></ul><ul><li> dose for less severe burns and non-intubated patients </li></ul><ul><ul><li>0.2 to 0.4 mcg/kg/hr for routine burn care </li></ul></ul><ul><ul><li>outpatient dressing changes, instead of ketamine </li></ul></ul>
    83. 83. Alcohol Withdrawal and Trauma <ul><li>Trauma often occurs in males who are intoxicated </li></ul><ul><li>Trauma pt may experience agitation and is at risk for exacerbating underlying injuries (e.g., SCI) </li></ul><ul><li>Benzodiazepines typically used </li></ul><ul><ul><li>Intubation and ventilation often required if extreme agitation </li></ul></ul><ul><li>Dexmedetomidine is an alternative </li></ul><ul><ul><li>Spontaneous breathing </li></ul></ul><ul><ul><li>Hemodynamic stability </li></ul></ul><ul><ul><li>Adequate sedation </li></ul></ul><ul><ul><li>Prevention of autonomic effects of withdrawal </li></ul></ul><ul><ul><li>Pain control </li></ul></ul>
    84. 84. Summary <ul><li>Goal is to establish + maintain adequate drug conc at effector site to produce desired effect </li></ul><ul><li>Dex can help optimize anesthesia via: </li></ul><ul><ul><li>Sedation, analgesia +  sympathetic activity </li></ul></ul><ul><ul><li>Attenuation of stress response +  HR </li></ul></ul><ul><ul><li>Smooth emergence + tracheal extubation </li></ul></ul><ul><li>Unique mechanism of action on natural sleep pathway permits sedation + analgesia w/o respiratory depression </li></ul><ul><li>Adjunct agent of choice for many surgeries </li></ul>
    85. 85. Thank You

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