Sedation.ppt

1、university of wisconsin madison, wi maine medical center portland, me university of wisconsin madison, wi participants should be able to: describe the sccm guidelines for sedation, analgesia, and chemical paralysis describe the benefits of daily awakening/lightening and sedation titration programs d

2、evise a rational pharmacologic strategy based on treatment goals and comorbidities participants should be able to: describe the sccm guidelines for sedation, analgesia, and chemical paralysis describe the benefits of daily awakening/lightening and sedation titration programs devise a rational pharma

3、cologic strategy based on treatment goals and comorbidities prevalence 50% incidence in those with length of stay 24 hours primary causes: unrelieved pain, delirium, anxiety, sleep deprivation, etc. immediate sequelae: patient-ventilator dyssynchrony increased oxygen consumption self (and health car

4、e provider) injury family anxiety long-term sequelae: chronic anxiety disorders and post- traumatic stress disorder (ptsd) some degree of recall occurs in up to 70% of icu patients. anxiety, fear, pain, panic, agony, or nightmares reported in 90% of those who did have recall. potentially cruel: up t

5、o 36% recalled some aspect of paralysis. associated with ptsd in ards? 41% risk of recall of two or more traumatic experiences. associated with ptsd in cardiac surgery factual memories (even unpleasant ones) help to put icu experience into perspective delusional memories risk panic attacks and ptsd

6、the optimal level of sedation for most patients is that which offers comfort while allowing for interaction with the environment. need for sedation anxiety pain acute confusional status mechanical ventilation treatment or diagnostic procedures psychological response to stress goals of sedation in ic

7、u patient comfort and control of pain anxiolysis and amnesia blunting adverse autonomic and hemodynamic responses facilitate nursing management facilitate mechanical ventilation avoid self-extubation reduce oxygen consumption lack of respiratory depression analgesia, especially for surgical patients

8、 rapid onset, titratable, with a short elimination half-time sedation with ease of orientation and arousability anxiolytic hemodynamic stability characteristics of an ideal sedation agents for the icu the challenges of icu sedation assessment of sedation altered pharmacology tolerance delayed emerge

9、nce withdrawal drug interaction sedation sedatives causes for agitation undersedation sedatives causes for agitation agitation 30:119-141. pain assess pain separately visual pain scales 0 1 2 3 4 5 6 7 8 9 10 no pain worst possible pain signs of pain hypertension tachycardia lacrimation sweating pup

10、illary dilation principles of pain management anticipate pain recognize pain ask the patient look for signs find the source quantify pain treat: quantify the patients perception of pain correct the cause where possible give appropriate analgesics regularly as required remember, most sedative agents

11、do not provide analgesia reassess nonpharmacologic interventions proper position of the patient stabilization of fractures elimination of irritating stimulation proper positioning of the ventilator tubing to avoid traction on endotracheal tube set goal for analgesia hemodynamically unstable fentanyl

12、 25 - 100 mcg ivp q 5-15 min, or hydromorphone 0.25 - 0.75 mg ivp q 5 - 15 min hemodynamically stable morphine 2 - 5 mg ivp q 5 - 15 min repeat until pain controlled, then scheduled doses + prn use pain scale * to assess for pain reassess goal daily, titrate and taper therapy to maintain goal, consi

13、der daily wake-up, taper if 1 week high-dose therapy 2:656-659 crit care med 1999;27:1325-1329 j clin psychopharmacol 1990;10:244-251 crit care med 1999;27:1271-1275 scaledescription 1anxious and agitated or restless, or both 2cooperative, oriented, and tranquil 3response to commands only 4brisk res

14、ponse to light glabellar tap or loud auditory stimulus 5sluggish response to light glabellar tap or loud auditory stimulus 6no response to light glabellar tap or loud auditory stimulus the ramsay scale score descriptiondefinition 7 dangerous agitation pulling at endotracheal tube, trying to strike a

15、t staff, thrashing side to side 6 very agitateddoes not calm despite frequent verbal commands, biting ett 5 agitatedanxious or mildly agitated, attempting to sit 4 calm and cooperative calm, awakens easily, follows commands 3 sedated difficult to arouse, awakens to verbal stimuli, follows simple com

16、mands 2 very sedatedarouse to physical stimuli, but does not communicate spontaneously 1 unarousableminimal or no response to noxious stimuli the riker sedation-agitation scale the motor activity assessment scale scoredescriptiondefinition 6 dangerous agitation pulling at endotracheal tube, trying t

17、o strike at staff, thrashing side to side 5 agitateddoes not calm despite frequent verbal commands, biting ett 4 restless and cooperative anxious or mildly agitated, attempting to sit 3 calm and cooperative calm, awakens easily, follows commands 2 responsive to touch or name opens eyes or raises eye

18、brows or turns head when touched or name is loudly spoken 1 responsive only to noxious stimuli opens eyes or raises eyebrows or turns head with noxious stimuli 0 unresponsivedoes not move with noxious stimuli what sedation scales do provide a semiquantitative “score” standardize treatment endpoints

19、allow review of efficacy of sedation facilitate sedation studies help to avoid oversedation what sedation scales dont do assess anxiety assess pain assess sedation in paralyzed patients predict outcome agree with each other bis monitoring bis monitoring bis range guidelines awake responds to loud co

20、mmands or mild prodding/shaking low probability to explicit recalls unresponsive to verbal stimuli burst suppression flat line eeg responds to normal voice axiolysis moderate sedation deep sedation 100 80 60 40 20 0 bis set goal for sedation acute agitation # midazolam 2 - 5 mg ivp q 5 - 15 min unti

21、l acute event controlled ongoing sedation # lorazepam 1 - 4 mg ivp q 10-20 min until at goal then q 2 - 6 hr scheduled + prn, or propofol start 5 mcg/kg/min, titrate q 5 min until at goal ivp doses more often than q 2hr? consider continuous infusion opiate or sedative 3 days propofol? (except neuro

22、pt.) convert to lorazepam benzodiazepine or opioid: taper infusion rate by 10-25% per day use sedation scale * to assess for agitation/anxiety lorazepam via infusion? use a low rate and ivp loading doses yes reassess goal daily, titrate and taper therapy to maintain goal, consider daily wake-up, tap

23、er if 1 week high-dose therapy lipid source (1.1 kcal/ml) respiratory depression propofol infusion syndrome -cardiac failure, rhabdomyolysis, severe metabolic acidosis, and renal failure -caution should be exercised at doses 80 mcg/kg/min for more than 48 hours -particularly problematic when used si

24、multaneously in patient receiving catecholamines and/or steroids sedation-agitation scale riker rr et al. crit care med. 1999;27:1325. alpha-2-adrenergic agonist like clonidine but with much less imidazole activity has been shown to decrease the need for other sedation in postoperative icu patients

25、potentially useful while decreasing other sedatives to prevent withdrawal benefits does not cause respiratory depression short-acting produces sympatholysis which may be advantageous in certain patients such as postop cardiac surgery risks no amnesia small number of patients reported distress upon r

26、ecollection of icu period despite good sedation scores due to excessive awareness bradycardia and hypotension can be excessive, necessitating drug cessation and other intervention benzodiazepines onsetpeaksduration diazepam2-5 min5-30 min20 hr midazolam2-3 min5-10 min30-120 min lorazepam5-20 min30 m

27、in10-20 hr propofol onsetpeaksduration propofol30-60 sec 2-5 minshort propofol dosing 3-5 g/kg/min antiemetic 5-20 g/kg/min anxiolytic 20-50 g/kg/min sedative hypnotic 100 g/kg/min anesthetic midazolampropofolopioids prolonged weaningx-x respiratory depressionx-x severe hypotensionxx- tolerancex-x h

28、yperlipidemia-x- increased infection-x- constipation-x lack of orientation and cooperation xxx problems with current sedative agents alpha-2 receptors brain (locus ceruleus) spinal cord peripheral vasculature sedation anxiolysis sympatholysis analgesia vasoconstriction dex: dosing loading infusion 0

29、.25-1 g/kg (10-20 min) maintenance infusion 0.2-0.7 g/kg/hr use continuous and combined infusion plasma level load maintenance repeated bolus plasma levels opioid + hypnotic infusion fentanyl + midazolam or propofol analgesia amnesia anxiolysis hypnosis continuous infusion regimens fentanyl 25-250 g

30、/h midazolam 0.5-5 mg/hr propofol 15-50 g/kg/min choose the right drug sedationanalgesia amnesiaanxiolysishypnosis propofol patient comfort benzodiazepines -2 agonists opioids altered pharmacology midazolam and age harper et al. br j anesth, 1985;57:866-871 delayed emergence overdose (prolonged infu

31、sion) pk derived from healthy patients drug interaction individual variation delayed elimination liver (cp450) kidney dysfunction active metabolites frequency related to dose and duration 32% if receiving high doses for longer than a week onset depends on the half-lives of the parent drug and its ac

32、tive metabolites clinical signs and symptoms are common among agents cns activation: seizures, hallucinations, gi disturbances: nausea, vomiting, diarrhea sympathetic hyperactivity: tachycardia, hypertension, tachypnea, sweating, fever no prospectively evaluated weaning protocols available 10 - 20%

33、daily decrease in dose 20 - 40% initial decrease in dose with additional daily reductions of 10 - 20% consider conversion to longer acting agent or transdermal delivery form seen in 50% of icu patients three times higher risk of death by six months five fewer ventilator free days (days alive and off

34、 vent.), adjusted p = 0.03 four times greater frequency of medical device removal nine times higher incidence of cognitive impairment at hospital discharge 1. acute onset of mental status changes or a fluctuating course 286: 2703-2710. no patient participation delirium screening checklist bergeron.

35、intensive care med. 2001;27:859. correct inciting factor, but as for painrelief need not be delayed while identifying causative factor control symptoms? no evidence that treatment reduces duration and severity of symptoms typical and atypical antipsychotic agents sedatives? - particularly in combina

36、tion with antipsychotic and for drug/alcohol withdrawal delirium no treatment fda approved no prospective randomized controlled trials in icu delirium 700 published reports involving 2,000 patients the good: hemodynamic neutrality no effect on respiratory drive the bad: qtc prolongation and torsades

37、 de pointes neuoroleptic malignant syndrome - only three cases with iv haloperidol extrapyramidal side effects - less common with iv than oral haloperidol mechanism of action unknown less movement disorders than haloperidol enhanced effects on both positive (agitation) and negative (quiet) symptoms

38、efficacy = haloperidol? one prospective randomized study showing equal efficacy of olanzapine to haldol with less eps issues lack of available iv formulation troublesome reports of cvas, hyperglycemia, nms titratability hampered - qtc prolongation with ziprasidone im - hypotension with olanzapine im

39、 used most often acutely (single dose) to facilitate intubation or selected procedures issues no analgesic or sedative properties concurrent sedation with amnestic effect is paramount analgesic as needed never use without the ability to establish and/or maintain a definitive airway with ventilation

40、if administering for prolonged period ( 6 - 12 hours), use an objective monitor to assess degree of paralysis. current use in icu limited because of risk of prolonged weakness and other complications maximize sedative/analgesic infusions as much as possible prior to adding neuromuscular blockade ind

41、ications facilitate mechanical ventilation, especially with abdominal compartment syndrome, high airway pressures, and dyssynchrony assist in control of elevated intracranial pressures reduce oxygen consumption prevent muscle spasm in neuroleptic malignant syndrome, tetanus, etc. protect surgical wo

42、unds or medical device placement two classes of nmbs: depolarizers - succhinylcholine is the only drug in this class - prolonged binding to acetylcholine receptor to produce depolarization (fasciculations) and subsequent desensitization so that the motor endplate cannot respond to further stimulatio

43、n right away nondepolarizers - blocks acetylcholine from postsynaptic receptor competitively - benzylisoquinoliniums curare, atracurium, cisatracurium, mivacurium, doxacuronium - aminosteroids pancuronium, vecuronium, rococuronium patients with aspiration risk need rapid onset paralysis for intubati

44、on. not usually used for continuous maintenance infusions rocuronium nondepolarizer with about an hour duration and 10% renal elimination dose is 1.2 mg/kg to have intubating conditions in 45 seconds succinylcholine depolarizer with a usual duration of 10 minutes all or none train of four after admi

45、nistration due to desensitization (can be prolonged in patients with abnormal plasma cholinesterase) dose is 1 - 2 mg/kg to have intubating conditions in 30 seconds increases serum potassium by 0.5 to 1 meq/liter in all patients can cause bradycardia, anaphylaxis, and muscle pain potentially increas

46、es intragastric, intraocular, and intracranial pressure severely elevates potassium due to proliferation of extrajunctional receptors in patients with denervation injury, stroke, trauma, or burns of more than 24 hours nondepolarizing muscle relaxants pancuronium, vecuronium, cisatracurium all rapid

47、onset (2 - 3 minutes) differ in duration (pancuronium 1 - 2 hours, vecuronium 0.5 hours, cisatracurium 0.5 hours) differ in route of elimination (pancuronium = renal/liver, vecuronium = renal/bile, cisatracurium = hoffman degradation) infusion doses pancuronium 0.05 - 0.1 mg/kg/h vecuronium 0.05 - 0

48、.1 mg/kg/h cisatracurium 0.03 - 0.6 mg/kg/h other distinguishing features pancuronium causes tachycardia vecuronium has neutral effects on hemodynamics but has several renally excreted active metabolites elimination of cisatracurium is not affected by organ dysfunction, but it is expensive goal - to

49、 prevent prolonged weakness associated with excessive nmba administration methods: perform nmba dose reduction or cessation once daily if possible clinical evaluation: assess skeletal muscle movement and respiratory effort peripheral nerve stimulation - train of four response consists of four stimul

50、ae of 2 hz, 0.2 msec in duration, and 500 msec apart. - comparison of t4 (4th twitch) and t1 with a fade in strength means that 75% of receptors are blocked. - only t1 or t1 and 2 is used for goal in icu and indicates up to 90% of receptors are blocked. bispectral index is based on cumulative observ

51、ation of a large number of clinical cases correlating clinical signs with eeg signals. while used to titrate appropriate sedation (and amnesia) in anesthetized patients to the least amount required, not proven to achieve this goal. increased potential for baseline neurologic deficit and eeg interfer

52、ence in icu patients no randomized controlled studies to support reliable use in icu. other neuromonitoring (awareness) modalities are likely to be developed. cessation of nmb as soon as safe in conjunction with other patient parameters should be a daily consideration. associated with inactivity: mu

53、scle wasting, deconditioning, decubitus ulcers, corneal drying associated with inability to assess patient: recall, unrelieved pain, acute neurologic event, anxiety associated with loss of respiratory function: asphyxiation from ventilator malfunction or accidental extubation, atelectasis, pneumonia

54、 other: prolonged paralysis or acute nmba related myopathy - related to decreased membrane excitability or even muscle necrosis - risk can be compounded by concurrent use of steroids. jacobi j, et al. crit care med. 2002;30:119-141. jones, et al. crit care med. 2001;29:573-580. cammarano, et al. cri

55、t care med. 1998;26:676. ely, et al. jama. 2004;292:168. 22-year-old male with isolated closed head injury who was intubated for gcs of 7 he received 5 mg of morphine, 40 mg of etomidate, and 100 mg of succinylcholine for his intubation. he is covered in blood spurting from an arterial catheter that

56、 was just removed, and he appears to be reaching for his endotracheal tube. what sedative would you use and why? what are the particular advantages in this situation? how could you avoid the disadvantages of this drug? propofol will rapidly calm a patient who is displaying dangerous behavior without

57、 need for paralysis. titratable and can be weaned quickly to allow for neurologic exam can treat seizures and elevated icp which may be present in a head trauma with gcs of eight or less minimizing dose and duration will avoid side effects. 54-year-old alcoholic who has been admitted for staph sepsi

58、s intubated in the icu for seven days and is currently on midazolam at 10 mg/hour his nurse was told in report that he was a “madman” on the evening shift. currently, he opens his eyes occasionally to voice but does not follow commands nor does he move his extremities to deep painful stimulation. is this appropriate sedation? what would you like to do? how would you institute your plan of action? this patient is overseda