Indications |
No "one size fits all" approach: positive indications only (cognitive, ventilatory, circulatory, renal, metabolic effects, absence of innate immuno-paralysis, etc.) |
Contraindications |
Sick sinus syndrome, spontaneous or drug-induced bradycardia, A-V block II/III, uncompensated hypovolemia, liver failure (consider clonidine), renal failure (consider dexmedetomidine unless renal replacement therapy is ongoing or considered) |
Drug selection |
Dexmedetomidine is easier to use (shorter half-life); clonidine is easier to use through the oral route in nonintubated patients with delirium tremens; clonidine or guanfacine p.o. transition from i.v. alpha-2 agonists |
|
Never use a bolus of alpha-2 agonist: place a "do not bolus" sticker on the iv line of the alpha-2 agonist(6565 Shehabi Y, Botha JA, Ernest D, Freebairn RC, Reade MC, Roberts BL, et al. Clinical application, the use of dexmedetomidine in intensive care sedation. Crit Care Shock. 2010;13(2):40-50.) |
1 Stable patient
|
Switching from conventional to cooperative sedation |
Abrupt withdrawal of conventional sedation followed immediately by i.v. infusion of alpha-2 agonist (dexmedetomidine 1.5μg.kg-1.h-1 or clonidine 2μg.kg-1.h-1 then titration to effect): expect 1 - 3 hours (dex) to 2 - 6 hours (clonidine) before reaching steady-state cooperative sedation |
Rescue sedation |
The administration of high dose alpha-2 agonist is suggested to reach steady state cooperative sedation as early as possible with minimal rescue sedation. Nevertheless, the dose of alpha-2 agonist has to be lowered to have an effect (-2 < RASS < 0) as early as possible |
Rescue sedation ready at hand in young combative patients: midazolam bolus 3 - 5mg (select the lowest dose; only bolus) to be repeated every 5 - 15 minutes if needed, up to steady-state cooperative sedation |
Titrate dexmedetomidine/clonidine to effect:-2 < RASS < 0; supportive therapy: early physiotherapy, sleep-wake cycle preservation, etc. |
Before nursing, if needed, consider midazolam bolus 3mg with reassurance. |
2 Unstable patient
|
Refractory delirium tremens |
Goal |
Supportive therapy as usual (hydration, potassium, magnesium, vitamins, etc.) |
Transient deeper sedation (RASS =-3) during cessation of agitation with alpha-2 agonists combined if needed with neuroleptics |
Then: quiet patient (-2 < RASS < 0): no brisk movement, agitation, hallucination, fine tremor for > 24 hours; as soon as agitation, hallucination, tremor is stopped for > 24 hours, consider tapering drug treatment over 48 - 96 hours |
Drug selection |
alpha-2 agonist ± neuroleptics (if needed very rarely: ± low-dose benzodiazepine: midazolam 0.5 - 1mg.h-1 ± baclofen) |
Discontinue benzodiazepine, opioid analgesics, etc., immediately upon admission; use benzodiazepines or opioid analgesics only as "rescue" sedation or "rescue" analgesia |
Nonintubated patient: clonidine p.o. 300 - 600μg in small amount of water every 4 hours, then every 6 hours, then every 8 hours, etc., up to 2 - 3μg.kg-1.h-1 for 72 - 96 hours. |
Intubated patient: |
Address volemia iteratively (see below) |
Dexmedetomidine 1.5μg.kg-1.h-1 or clonidine 2μg.kg-1.h-1 |
Place a "do not bolus" sticker on the i.v. line(6565 Shehabi Y, Botha JA, Ernest D, Freebairn RC, Reade MC, Roberts BL, et al. Clinical application, the use of dexmedetomidine in intensive care sedation. Crit Care Shock. 2010;13(2):40-50.) |
When alpha-2 agonists are not sufficient to evoke-2 < RASS < 0 with absence of brisk movement agitation or tremor, supplement with neuroleptics |
a) Hallucinations: haloperidol bolus 5 - 10 mgx4 or 50mg/48mL/24 hours: 2mg.h-1 to be lowered as soon as RASS <-2 |
NB: consider haloperidol maximal dose: 30mg.d-1;(9393 Carrasco G, Baeza N, Cabré L, Portillo E, Gimeno G, Manzanedo D, et al. Dexmedetomidine for the treatment of hyperactive delirium refractory to haloperidol in nonintubated ICU patients: a nonrandomized controlled trial. Crit Care Med. 2016;44(7):1295-306.) some authors use significantly higher doses |
b) Agitation: loxapine 100mgx4 through nasogastric tube to be lowered to 75mgx4, then 50mgx4, etc., and stopped as soon as possible |
Administer neuroleptic as first-line drug (e.g., haloperidol 5mg i.v. or loxapine 100mg through the nasogastric tube) to avoid abrupt agitation upon withdrawal of conventional sedation and before achieving steady-state cooperative sedation; suppress neuroleptics to make treatment as simple as possible as soon as possible |
NB: monitor QT when administering any neuroleptics |
Tracheal extubation |
Alpha-2 agonists do not suppress airway reflexes: a) assess clinical status (ventilation, circulation, infection, inflammation, etc.); b) taper neuroleptics first; c) titrate alpha-2 agonists to-2 < RASS < 0, then extubate under continued administration of alpha-2 agonist titrated to-2 < RASS < 0 |
Tapering alpha-2 agonists |
Alpha-2 agonist withdrawal is of rare occurrence: nevertheless, taper i.v. or p.o. alpha-2 agonist over 48 - 96 hours; clonidine p.o. or guanfacine p.o are useful here |
Discharge from CCU |
Do not discharge the patient early to ward (hallucinations or tremor should be suppressed for > 24 hours): alpha-2 agonists are usually withdrawn on the ward with reintroduction of benzodiazepines, leading to readmission to CCU |
Shock/circulatory distress |
Address hypovolemia iteratively |
Iterative passive leg raising (PLR, figure 1(121121 Monnet X, Teboul JL. Passive leg raising. Intensive Care Med. 2008;34(4):659-63.)) and echocardiography (collapsability of vena cava, etc.; see text) to allow for absence of increase in systemic pressure or in cardiac output following volume loading (e.g., crystalloid bolus 1000mL/70kg patient) |
Volume loading (1000mL bolus/70kg) as long as there is hypovolemia (a pressure or better a cardiac output response to PLR does not necessarily mean that the patient is hypovolemic; figure 1).(122122 Monnet X, Teboul JL. Passive leg raising: five rules, not a drop of fluid! Crit Care. 2015;19(1):18.) The lung is to be kept “dry”. |
Objective: maintenance of stroke volume,(109109 Morelli A, Sanfilippo F, Arnemann P, Hessler M, Kampmeier TG, D’Egidio A, et al. The effect of propofol and dexmedetomidine sedation on norepinephrine requirements in septic shock patients: a crossover trial. Crit Care Med. 2019;47(2):e89-e95.) diuresis, suppression of mottling, normalization of capillary refill time, lactate, CO2 gap, and SsvcO2
|
"Start slow, go slow": dexmedetomidine 0.125μg.kg-1.h-1 for 1 h, then increments of 0.125 to 0.375μg.kg-1.h-1 every hour, up to 1.5μg.kg-1.h-1, according to iterative PLR, echocardiography and circulatory response; rescue sedation only if agitation |
Or clonidine 0.125μg.kg-1.h-1 for 1 h, then increments of 0.125 to 0.375μg.kg-1.h-1 every h, up to 2μg.kg-1.h-1, according to iterative PLR, echocardiography and circulatory response, rescue sedation if agitation |
Vasopressors and inotropes according to the usual clinical and echocardiographic indications; no increase in vasopressor or inotrope requirement is observed unless hypovolemia or ventricular failure is not addressed before and during initiation of cooperative sedation |
Antiarrhythmics (amiodarone, verapamil, beta blockers, etc.) are used as indicated if dosage and speed of administration are reduced by 50-75% |
Ventilatory distress without circulatory distress |
|
Discontinue conventional sedation abruptly; if needed, rescue sedation immediately available to maintain-2 < RASS < 0 |
Address all causes of tachypnea/hyperpnea: fever control, agitation, inflammation, lung water, systemic acidosis, poor microcirculation, capnia, and hypoxemia |
Address iteratively volemia and circulatory function: see circulatory distress |
Dexmedetomidine 1.5μg.kg-1.h-1 or clonidine 2μg.kg-1.h-1 then titrated to-2 < RASS < 0 |
Acute cardioventilatory distress |
|
Beyond the goal of the paper aiming at junior staff: stabilize circulation first or ventilation first depending of the clinical situation, and then switch from conventional to cooperative sedation in an itemized manner: "start slow, go slow", as described above, in an overtly cautious manner |
Antinociception |
|
Following steady state cooperative sedation, assess pain: visual analog scale (nonintubated patient) or behavioral pain scale (intubated patient); "medical" patients need little antinociception; "surgical" patients require more antinociception |
Nonopioid analgesia |
As alpha-2 agonists provide analgognosia and analgesia without respiratory depression, the use of opioids with a respiratory depressant effect appears counterproductive |
a) Ketamine 50 - 100mg.day-1, tramadol 400mg.day-1, nefopam 100mg.day-1/48mL: 2mL.h-1. These dosages are to be reduced by 50 - 75% after 1 - 3 days of full impregnation with an alpha-2 agonist |
NB: in elderly patients administer nefopam 20mg/day for 1 - 2 days, and then increase nefopam if necessary up to 100mg if no cognitive side-effects occur; beware of possible acute urine retention if Foley catheterization is not performed |
NB: tramadol is a weak opioid analgesic acting on μ receptors and is contraindicated if acute kidney insufficiency is present |
To avoid opioid analgesics completely or to stop the administration of tramadol-nefopam early in elderly patients, consider |
b) Amitryptyline (Laroxyl®) 25mg i.v.x4 or lidocaine 0.5mg/kg/h (loading dose: 1mg. kg-1.h-1) or ketamine (0.25mg kg-1.h-1) infusion |
c) Or pregabaline (Lyrica®) 150 - 600mg/day: start with 25mgx2 through n/g (Day 0), then 50 x 2 (Day 2), 75x2 (Day 3), etc.; in the case of pancreatitis or CCU neuromyopathy, consider 150 x 2 up to a total daily dose of 600mg |
c) Gabapentine (Neurontin® 100 - 900mg/day) or carbamazepine (Tegretol® 200 - 400mg/day) |
Rescue opioids |
Only if needed, after pain assessment, rescue opioid analgesics to be reintroduced sparingly aiming for early spontaneous ventilation, intestinal motility, absence of hyperalgesia |
B: De novo cooperative sedation |
Indications |
No "one size fits all" approach: positive indications only (cognitive, ventilatory, circulatory, renal, metabolic effects; absence of innate immune paralysis, etc.) |
Contraindications |
Sick sinus syndrome, bradycardia (spontaneous or drug-induced), A-V block II/III, uncompensated hypovolemia, liver failure (consider clonidine), renal failure (consider dexmedetomidine unless renal replacement therapy is ongoing or considered) |
Drug selection |
Dexmedetomidine is easier to use (shorter half-life); clonidine is easier to use when the oral route is possible (nonintubated patients with delirium tremens); clonidine or guanfacine transition from i.v. alpha-2 agonists to no therapy |
|
Place a "do not bolus" sticker on the i.v. line: never use a bolus of alpha-2 agonist |
Circulatory distress |
|
Address volemia and circulation iteratively: A |
Start slow and go slow to administer alpha-2 agonist: A |
Have rescue and breakthrough sedation immediately available: A |
Address volemia before general anesthesia, endotracheal intubation and positive-pressure ventilation+PEEP: consider volume (1000mL/70kg patient)(163) |
Consider very high O2 flow or noninvasive ventilation: oxygenation and suppressed work of breathing (patient-self induced lung injury) prior to intubation |
Dexmedetomidine 1.5μg.kg-1.h-1 or clonidine 2μg.kg-1.h-1 then titrated to-2 < RASS < 0, immediately following noninvasive ventilation or invasive ventilation |
Antinociception |
|
Assess pain: visual analog scale in nonintubated patient or behavioral pain scale in intubated patient |
Drugs: priority to nonopioid analgesics; use rescue opioid analgesics only; table A |