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在加護病房、重症的病人上，常常會有PADIS的問題

什麼是PADIS？
= 疼痛(Pain)
= 躁動(Agitation)
= 譫妄(Delirium)
= 不動(Immobility)
= 睡眠中斷(Sleep disruption)

重點：
• 嗎啡是很好的止痛藥物
(Morphine sulfate is the preferred analgesic agent for critically ill patients.)
• 對於血行動力學不穩定的病人，芬太尼是很好的選擇，相比於嗎啡，也比較少見組織胺的釋放或過敏反應
(Fentanyl is the preferred analgesic agent for critically ill patients with hemodynamic instability, for patients manifesting symptoms of histamine release with morphine or morphine allergy.)
• 二氫嗎啡酮是嗎啡的另外一個選擇
(Hydromorphone can serve as an acceptable alternative to morphine.)
•咪達唑侖和異丙酚建議用於重症病人短期的焦慮處理
(Midazolam or propofol are the preferred agents only for preferred agents only for the short-term (less than 24) treatment of anxiety in the critically ill adult.)
• 蘿拉西泮建議用於需要長期治療的焦慮
(Lorazepam is the preferred agent for prolonged treatment of anxiety in the critically.)
• 氟哌啶醇建議用於瞻望治療
(Haloperidol is the preferred agent for treatment of delirium in the critically ill adult.)

Shapiro PA, et al. Crit Car Med. 1995; 23(9):1596-1600.

Pain (Assessment)
1.What are the most valid and reliable measures of pain in critically ill adult patients regardless of whether the patient is under mechanical ventilation?
-For patients who can self-report, either the Numeric Rating Scale (NRS) or the Visual Analogue Scale (VAS) is recommended, target score for pain alleviation is NRS < 4 or VAS < 3.
-For patients who cannot self-report, Behavioral Pain Scale (BPS) or the Critical-Care Pain Observation Tool (CPOT) is recommended, target score for pain alleviation is BPS < 5 or CPOT <3.
“Caution: The validity and reliability should be reassessed after Chinese translation of these tools.
2.Should vital signs be used to assess pain in adult ICU patients?
-We do not suggest that vital signs (or observational pain scales that include vital signs) be used alone for pain assessment in adult ICU patients.
-We suggest that vital signs may be used as a cue to begin further assessment of pain in these patients.

疼痛評分量表(Screening Tools for Pain Assessment)

BPS

BPS-NI

CPOT

Pain (Treatment)
1.Should procedure-related pain be treated pre-emptively in adult ICU patients?
-We recommend that for all potentially painful procedures in adult ICU patients, pre-emptive analgesic therapy and/or non-pharmacologic interventions may also be administered to alleviate pain.
2.What types of medications should be administered for pain relief in adult ICU patients?
-All available IV opioids could be considered as the first-line drug class of choice to treat non-neuropathic pain in critically ill patients.
-Either enterally administered gabapentin or carbamazepine, in addition to IV opioids, could be considered for the treatment of neuropathic pain.
“Caution: Use HLA-B 1502 gene screening before administration of carbamazepine to avoid Steven-Johnson syndrome or toxic epidermal necrolysis.
-Non-opioid analgesics could be considered to decrease the amount of opioids administered (or to eliminate the need for IV opioids altogether) and to decrease opioid-related side effects.
3.What mode of analgesic delivery is recommended for pain relief in critically ill adults who have undergone either abdominal aortic surgery or traumatic rib fractures?
-Thoracic epidural anesthesia could be considered for post-operative analgesia for abdominal aortic surgery or traumatic rib fracture.

Agitation (Assessment)
1.Should adult ICU patients be maintained at a light level of sedation?
-The patient's outcome (such as shortening ventilator days and ICU stay) can be improved by maintaining light sedation unless contraindicated.
-The stress response of the patient may be increased by maintaining light sedation, but the frequency of myocardial ischemia is not affected.
2.Which subjective sedation scales are the most valid and reliable in the assessment of depth and quality of sedation in mechanically ventilated adult ICU patients?
-The Richmond Agitation-Sedation Scale (RASS) and the Sedation-Agitation Scale (SAS) are the most useful scales for assessing sedation depth and quality in adult patients.
-Other sedation scales (such as Ramsay scale) can be used according to the hospital policy.
3.Should objective measures of brain function (e.g., auditory evoked potentials (AEPs), bispectral index (BIS), Narcotrend index (NI), patient state index (PSI), or state entropy (SE)) be used to assess depth of sedation in non-comatose, adult ICU patients who are not receiving neuromuscular blocking agents?
-We do not recommend that objective measures of brain function (e.g. AEPs, BIS, NI, PSI, or SE) be used as the primary measure to monitor the depth of sedation in non-comatose, non-paralyzed critically ill adult patients, as these monitors are inadequate substitutes for subjective sedation scoring systems.
4.Should objective measures of brain function (e.g. AEPs, BIS, NI, PSI, or SE) be used to measure depth of sedation in adult ICU patients who are receiving neuromuscular blocking agents?
-When the neuromuscular blocking agents is used and the subjective assessment of a patient is difficult, the use of an objective index such as the auxillary sedation depth assessment is suggested.
5.Should EEG monitoring be used to detect non-convulsive seizure activity and to titrate electrosuppressive medication to obtain burst suppression in adult ICU patients with either known or suspected seizures?
-The EEG (30 minutes or continuous) monitoring could be consider in the ICU patients with suspected or known risk factors of non-convulsive seizures.

“Risk factors of agitation”
......a. Coma of unknown causes
......b. Inadequate treatment of generalized status epilepticus
......c. History of epilepsy
......d. Encephalopathic
......e. Electrolyte abnormality
......f. Infections state
......g. Glucose dysregulation

Ramsay Sedation Scale

Riker Sedation-Agitation Scale (SAS)

Richmond Agitation Sedation Scale (RASS)

Agitation (Treatment)
1.Should non-benzodiazepine (BZD)-based sedation, instead of sedation with benzodiazepines, be used in mechanically ventilated adult ICU patients?
-We suggest that sedation strategies using non-BZD sedatives could be chosen to improve clinical outcomes in mechanically ventilated adult ICU patients.
-Triglyceride concentrations should be monitored after >2 days of propofol infusion, and total caloric intake form lipids should be included in the nutrition support prescription.
-The potential for opioid, BZD and propofol withdrawal should be considered after high doses or more than 7 days of continuous therapy.
-Doses should be tapered systematically to prevent withdrawal symptoms.
2.Which sedative is more effective for adult patients under artificial respiration, dexmedetomidine or propofol?
-As of now, the relative superiority of dexmedetomidine or propofol as a sedative for adult patients under mechanical ventilation cannot be determined due to lack of evidence.
3.Should a protocol that includes either daily sedative interruption or a light target level of sedation be used in mechanically ventilated adult ICU patients?
-Unless having obvious contra-indications, we recommend either daily sedation interruption or a light target level of sedation be routinely used in mechanically ventilated adult ICU patients.
4.Should analgesia-first sedation (i.e., analgosedation) or sedative-hypnotic-based sedation be used in mechanically ventilated ICU patients?
-We suggest that analgosedation be used in mechanically ventilated adult ICU patients.

Sleep disorder
=Should non-pharmacologic interventions be used to promote sleep in adult ICU patients?
-We recommend multi-faceted measures to improve sleep quality in adult ICU patients by optimizing patients' environments, using strategies to control light and noise, clustering patient care activities, and decreasing stimuli at night to protect patients' sleep cycles.

Delirium (Assessment)
1.What outcomes are associated with delirium in adult ICU patients?
-Delirium worsens the prognosis of patients in ICUs.
-Delirium prolongs the duration of stay in ICUs.
-Delirium influences subsequent cognitive dysfunction outside the ICU.
2.Should ICU patients be monitored routinely for delirium with an objective bedside delirium instrument?
-We encourage routine monitoring of adult ICU patients for the symptoms of delirium with an objective instrument.
3.Which instruments available for delirium monitoring have the strongest evidence for validity and reliability in ventilated and non-ventilated medical and surgical ICU patients?
-The Confusion Assessment Method for Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) are the most valid and reliable delirium monitoring tools for ICU patients.
4.Is implementation of routine delirium monitoring feasible in clinical practice?
-The delirium monitoring of adult ICU patients can be practiced routinely.

“Risk factors of delirium”
……a. pre-existing dementia
……b. history of hypertension
……c. alcoholism
……d. high severity of illness at admission
……e. coma
……f. opioid use
……g. benzodiazepine use

Delirium (Prevention)
1.Should early mobilization be used in the ICU to reduce the incidence or duration of delirium?
-We recommend performing early mobilization of adult ICU patients whenever feasible to reduce the incidence and duration of delirium.
2.Should haloperidol or atypical antipsychotics be used prophylactically to prevent delirium in ICU patients?
-We do not suggest that either haloperidol or atypical antipsychotics be administered to prevent delirium in adult ICU patients.
3.Should dexmedetomidine be used prophylactically to prevent delirium in ICU patients?
-We provide no recommendation for the use of dexmedetomidine to prevent delirium in adult ICU patients, as there is no evidence regarding its effectiveness in these patients.
4.Is there non-pharmacologic prevention for high risk patient?
-Reduce or shorten delirium: Re-orientation, cognitive stimulation, use of clocks
-Improve sleep: Minimizing light and noise
-Improve wakefulness: Reduce sedation
-Reduce immobility: Early rehabilitation/mobilization
-Reduce hearing and visual impairment: Enable use of devices such as hearing aids or eye glasses

Delirium (Treatment)
1.What baseline risk factors are associated with the development of delirium in the ICU?
-Baseline risk factors are as following: age; a high severity of illness; infection (septicemia); pre-existing dementia; and history of alcoholism.
2.Which ICU treatment-related (acquired) risk factor (I.e., opioids, benzodiazepines, propofol, and dexmedetomidine) are associated with the development of delirium in adult ICU patients?
-Benzodiazepine (BZD) use may be a risk factor for the development of delirium.
-Conflicting datat surround the relationship between opioid use and delirium.
-Dexmedetomidine infusion may be associated with a lower prevalence of delirium compared to BZD infusions in mechanically ventilated adult ICU patients at risk for developing delirium.
3.Does treatment with haloperidol reduce the duration of delirium in adult ICU patients?
-There is no published evidence that treatment with haloperidol reduces the duration of delirium.
4.Does treatment with atypical antipsychotics reduce the duration of delirium in adult ICU patients?
-Atypical antipsychotics may reduce the duration of delirium.
5.Should treatment with cholinesterase inhibitors (rivastigmine) be used to reduce the duration of delirium in ICU patients?
-We do not recommend administering rivastigmine to reduce the duration of delirium in ICU patients.
6.Should haloperidol and atypical antipsychotics be withheld in patients at high risk for torsades de pointes?
-We do not suggest using antipsychotics in patients at significant risk of torsades de pointes (i.e., prolong of QT interval, receiving concomitant medication known to prolong the QT interval, or patients with a history of this arrhythmia).
7.For mechanically ventilated, adult ICU patients with delirium who require continuous IV infusions of sedative medications, is dexmedetomidine preferred over BZD to reduce the duration of delirium?
-We suggest that in adult ICU patients with delirium unrelated to alcohol or BZD withdrawal, continuous IV infusions of dexmedetomidine may be better than BZD infusions to reduce the duration of delirium.

8.What is propofol related infusion syndrome (PRIS)?
-Rare complication (<1%), high mortality (33~66%)
-High doses (>4mg/kg/hr), prolonged use (>48hrs)
-Risk factors: young age, critical illness, high fat and low carbohydrate intake, inborn eroors of mitochondrial fatty acid oxidation, concomitant catecholamine infusion or steroid therapy
-Characteristics of PRIS: acute refractory bradycardia, severe metabolic acidosis, cardiovascular collapse, rhabdomyolysis, hyperlipidemia, renal failure, hepatomegaly