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
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
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27. DXMD produces st-2 of NREM sleep by removing the inhibitory impulse from LC inhibition uninhibited Anesthesiology 2003; 98:428–36
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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. DXMD: Predictable Hemodynamic Responce Ebert et al. Anesthesiology. August 2000; 93(2):382-394 Plasma Dexmedetomidine (ng/mL) 0.9ng/ml with 1mcg/kg
54. Potential role of DXMD for sedation in the Intensive Care Unit BUMC PROCEEDINGS 2001;14:13–21
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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
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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.
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
