Daily ICU Sedation Holidays

Published

Kress JP, et al. "Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation". The New England Journal of Medicine. 2000. 342(20):1471-1477.
PubMed • Full text • PDF

Clinical Question

Among medical ICU patients on mechanical ventilation requiring continuous sedation, do daily sedation holidays reduce days intubated, in the ICU, or in the hospital when compared to physician-guided sedation holidays?

Bottom Line

Daily sedation holidays reduce days on mechanical intubation, days in ICU, and days in the hospital when compared to physician-directed holidays.

Major Points

Continuous sedative infusions reduce anxiety, decrease oxygen consumption, and reduce nursing requirements among mechanically ventilated ICU patients. However, there had been concerns that continuous sedation led to extended courses of mechanical intubation given the inability to assess patients' overall mental capacity (including detection of new neurologic events) and potential for accumulation of sedatives.

Published in 2000, this single-center study by Kress, et al., randomized 128 intubated ICU patients to either daily interruptions of sedation (commonly known as "sedation holidays") or interruptions when thought to be appropriate by the intensivist. Of note, the daily sedation interruptions included evaluation by the clinician to assess for appropriateness for continuation of sedation. Daily sedation holidays were associated with a decreased duration of mechanical ventilation by 2.8 days and time in the ICU by 3.5 days. There was no mortality benefit.

Two related studies extend on the findings of this trial. First, the 2008 Awakening and Breathing Controlled Trial evaluated a "wake up and breathe" protocol that followed daily sedation holidays with spontaneous breathing trials (SBT). This technique reduced time on a ventilator, days in the ICU, and days in the hospital when compared to usual sedation techniques and daily SBTs. Second, the single-center Danish No Sedation in ICU Patients trial published in 2010 by Strøm et al. likewise demonstrated reduced time on a ventilator, days in the ICU, and days in the hospital when compared to a sedation holiday protocol. A multicenter trial to confirm these outcomes is lacking.

Guidelines

SCCM Pain, Agitation, and Delirium in the ICU (2013)

• Recommend daily sedation interruption or light target level of sedation for adult ICU patients on mechanical ventilation (strength 1, evidence B)
• Suggest sedation using the non-benzodiazepine sedatives propofol or dexmedetomidine to improve clinical outcomes for adult ICU patients on mechanical ventilation (strength 2, evidence B)

IHI Ventilator Bundle (2011)

• Peptic ulcer disease prophylaxis
• Elevation of the head of the bed
• Daily sedation vacations and assessment for extubation readiness
• DVT prophylaxis
• Daily oral care with chlorhexidine

Surviving Sepsis Campaign severe sepsis and septic shock (2016, adapted)

• Recommend spontaneous breathing trials in patient with sepsis on a mechanical ventilator who are ready for weaning (strong recommendation, high quality of evidence)

Recommend continuous or intermittent sedation be minimized in patients with sepsis on mechanical ventilations, targeting specific titration end points (best practice statement)

Design

• Single center, randomized, open-label study
• N=128
  • Interruption (n=68)
  • Continuous sedation (n=60)
• Setting: A single medical ICU in Chicago
• Enrollment: Not explicitly stated
• Mean follow-up: Not explicitly stated
• Analysis: Intention-to-treat
• Primary outcomes:
  • Duration of mechanical ventilation
  • Duration of ICU stay
  • Duration of hospitalization

Population

Inclusion Criteria

• Adult medical ICU patients receiving mechanical intubation
• Thought to require continuous sedative infusion (ie, agitation or discomfort after recovering from intubation)

Exclusion Criteria

• Pregnancy
• Transfer from an outside hospital where sedatives have already been given
• Admission for cardiac arrest
• Those enrolled were excluded from the analysis if died or successfully extubated in first 48 hours or if extubated before weaning of sedation

Baseline Characteristics

From the interruption group.

• Demographics: Age 57 years, male 50%
• Health data: Weight 70 kg
• Critical illness data: APACHE II score 20, permissive hypercapnea 18%
• Diagnosis: ARDS or pulmonary edema 29%, COPD or respiratory failure 32%, asthma 6%, sepsis 15%, delirium 12%, hemorrhagic shock 1%, cardiogenic shock 3%, drug overdose 1%
• Additional therapies: Cisatracurium 10%

Interventions

• Randomization to either interruption or continuous sedation group.
  • Interruption: Daily cessation of sedative infusion 48 hours after enrollment
    • Goal arousal was to the point at which a patient was able to follow instructions or was deemed in enough discomfort or agitation to require reinitiation of treatment
    • A physician assessed the patient at goal arousal and chose whether to continue sedation
  • Continuous sedation: Cessation of sedative infusion at the discretion of the staff
• Groups were further randomized to either propofol or midazolam for nonanalgesic therapy
• Analgesic therapy was provided by morphine
• Cisatracurium was used as a paralytic to patients with ARDS or status asthmaticus with ineffective ventilation
• Daily assessment of baseline level of arousal gauged by the ability to follow commands to open eyes, track with eyes, squeeze hands, or protrude the tongue

Outcomes

Comparisons are interruption vs. continuous sedation except where specified.

Primary Outcomes

Duration of mechanical ventilation

4.9 vs. 7.3 days (P=0.004)

Duration of ICU stay

6.4 vs. 9.9 days (P=0.02)

Duration of hospitalization

13.3 vs. 16.9 days (P=0.19)

Secondary Outcomes

All-cause mortality

36% vs. 47% (P=0.25)

Withdrawal of care: 35% vs. 42% (P=1.00)

Discharge the patient's home

59% vs. 40% (P=0.06)

No awakening during stay

10% vs. 25% (P=0.05)

Reintubation

18% vs. 30% (P=0.17)

Tracheostomy

18% vs. 27%

Cessation of continuous sedation group's sedatives except on final day of administration

30%

Subgroup Analysis

Dose of sedative

Midazolam: 230 vs. 425 mg (P=0.05)

Propofol: 15.1 vs. 17.6 kg (P=0.54)

Rate of sedative

Midazolam: 0.032 vs. 0.054 mg/kg/hr (P=0.06)

Propofol: 1.9 vs. 1.4 mg/kg/hr (P=0.004)

Dose of morphine

Midazolam: 205 vs. 481 mg (P=0.009)

Propofol: 352 vs. 382 mg (P=0.33)

Rate of morphine

Midazolam: 0.027 vs. 0.05 mg/kg/hr (P=0.004)

Propofol: 0.035 vs. 0.043 mg/kg/hr (P=0.65)

Criticisms

• Not blinded
• High rate of sedation interruption in the continuous sedation group
• No surgical ICU patients included
• The authors do not explicitly state that the total dose of sedatives in the interruption group may be responsible for the improved outcome -- the continuous sedation group may have received too much sedation
• No analysis of patient discomfort, device removal, or patient recall
• Power too low to detect complications like self extubations
• No assessment of cardiovascular endpoints

Funding

Not explicitly stated.