Both severe pain and opioid therapy are associated with negative effects. The experience of pain is common in the intensive care unit, but it is highly individual and difficult to assess, as patients are often unable to communicate. This especially applies to patients who are mechanically ventilated. Behavioral assessment tools can help to identify pain in this population, but do not register overdose of opioid therapy. The AlgiScan® delivers the Pupillary Pain Index (PPI), an objective assessment of nociception level, which has been shown to be useful in small studies with respect to reduction of opioid dose without leading to more pain. New institutional protocols for the assessment of pain include the behavioral pain assessment tool Zurich Observational Pain Assessment (ZOPA) and the PPI. This project aims to evaluate the impact of the new institutional protocols on opioid administration and occurrence of pain compared to a historical cohort by analyzing routinely collected data during mechanical ventilation (Part A). In a second part (Part B), promising biomarkers for detection of pain, subjective ratings by nurses and physicians and an additional behavioral pain scale will be evaluated using an observational study design. After screening and enrolment (day 1/visit 1), characteristics of pain will be assessed on 4 occasions during 2 days (day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5). On visit 2 and 4, biomarkers (alpha-amylase, cortisol) will be sampled.
Study Type
OBSERVATIONAL
Enrollment
400
University Hospital Zurich
Zurich, Canton of Zurich, Switzerland
Oral morphine equivalent (OME) per day of mechanical ventilation.
OME is a standardized method to quantify and compare the potency of different opioid drugs by converting their doses into the equivalent amount of oral morphine. Doses are weighted based on the potency of the opioid and then summarized into a final value. Days of mechanical ventilation are weighted based on the hours of mechanical ventilation divided by 24 hours (relevant for days of intubation and extubation).
Time frame: Part A: during mechanical ventilation (up to 28 days)
Sufentanil dose per day of mechanical ventilation
average dose \[mcg/min\]
Time frame: Part A: during mechanical ventilation (up to 28 days)
Opioid dose adjustments - Number of adjustments
Number of dose adjustments \[/hour\] and direction
Time frame: Part A: during mechanical ventilation (up to 28 days)
Opioid dose adjustments - Relative change during pain assessment
Relative change of dose 45min after vs. 15min before ZOPA/PPI
Time frame: Part A: during mechanical ventilation (up to 28 days)
Zurich Observational Pain Assessment (ZOPA)
The Zurich Observational Pain Assessment (ZOPA) is a validated behavioural pain assessment tool routinely used in the intensive care unit. The ZOPA includes 13 items in 4 categories. Each item is rated on a binary scale (yes or no), resulting in a minimum of zero and a maximum of 13 points. One or more positive item (meaning the item is rated with "yes") is interpreted as probable existing pain.
Time frame: Part A: during mechanical ventilation Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Number of rescue analgesics administered per day
Bolus administration of opioids
Time frame: Part A: during mechanical ventilation (up to 28 days)
Occurrence of adverse effects of pain per day of mechanical ventilation
* Intravenous antihypertensive treatment \[y/n\] * Atrial fibrillation \[y/n\] * anti-infective treatment \[y/n\] * Richmond Agitation Sedation Scale (RASS) \> +1 \[y/n\]
Time frame: Part A: during mechanical ventilation (up to 28 days)
Number of sedatives used per day of mechanical ventilation
Average number of sedatives used in the intensive care unit (e.g. Propofol, Clonidine, Dexmedetomidine, Ketamine, Sevoflurane and Midazolam)
Time frame: Part A: during mechanical ventilation (up to 28 days)
Richmond Agitation Sedation Scale (RASS) < -3
Duration of Richmond Agitation Sedation Scale (RASS) \< -3 per total ventilation days. The RASS is a validated 10-point scale with a range from -5 (unarousable) to +4 (combative), with 0 being "alert and calm".
Time frame: Part A: during mechanical ventilation (up to 28 days)
Time to extubation
Time to extubation from stop of analgosedation \[hours\]
Time frame: Part A: From time of stop of analgosedation (during mechanical ventilation, up to 28 days) until extubation (up to 7 days). Events such as death or referrals while being intubated will be censored.
Opioid prescription at ICU discharge
\- Opioid prescription at ICU discharge \[y/n\] in patients discharged alive (as listed in the ICU discharge report)
Time frame: Part A: at ICU discharge assessed up to 5 days
Opioid prescription at hospital discharge
\- Opioid prescription at hospital discharge \[y/n\] in patients discharged alive (as listed in the hospital discharge report)
Time frame: Part A: at hospital discharge assessed up to 10 days
Target nociception level
Target Pupillary Pain Index. The Pupillary Pain Index (PPI) is a scale with range from 1 to 9 indicating the pupillary response to a noxious stimulus. A lower value indicates a deeper nociception level (a more intense stimulus is necessary to trigger pupillary dilation). A higher value indicates a lighter nociception level (a less intense stimulus triggers pupillary dilation).
Time frame: Part A: during mechanical ventilation (up to 28 days)
Opioid-free days in the ICU
Days free of opioid administration \[%\]
Time frame: Part A: from ICU admission to ICU discharge (up to 100 days)
Pupillary Pain Index
Objective pain measurement of nociception level. The Pupillary Pain Index (PPI) is a scale with range from 1 to 9 indicating the pupillary response to a noxious stimulus. A lower value indicates a deeper nociception level (a more intense stimulus is necessary to trigger pupillary dilation). A higher value indicates a lighter nociception level (a less intense stimulus triggers pupillary dilation).
Time frame: - Part A: During mechanical ventilation - Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Cortisol
blood and saliva levels \[nmol/L\]
Time frame: Part B: day 2/visit 2, day 3/visit 4
Amylase
blood and saliva \[U/L\]
Time frame: Part B: day 2/visit 2, day 3/visit 4
Critical Care Pain Observation Tool (CPOT)
Validated behavioural pain assessment tool used in other intensive care units. The CPOT evaluates 4 dimensions. A score of 2 or less is regarded as likely minimal to no pain. A score of more than 2 is regarded as unacceptable level of pain.
Time frame: Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Subjective pain rating
Questionnaire based rating of pain \[y/n\] by physician and nurses
Time frame: Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Subjective rating of nociception level
Questionnaire based rating of nociception level \[light/moderate/deep\] by physician and nurses: * light: moderate stimulus triggers pain * moderate: strong stimulus triggers pain * deep: strong stimulus does not trigger pain * Rated by physicians and ICU nurses
Time frame: Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Trust in the Zurich Observational Pain Assessment (ZOPA)
Trust rated by ICU physicians and ICU nurses on a numeric scale with a range from 0 to 10. 0 indicates no trust in the ZOPA and 10 indicates maximal trust in the ZOPA.
Time frame: Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Trust in the Pupillary Pain Index (PPI)
Trust rated by ICU physicians and ICU nurses on a numeric scale with a range from 0 to 10. 0 indicates no trust in the PPI and 10 indicates maximal trust in the PPI.
Time frame: Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5
Pupil size before stimulation
Pupil size before stimulation PPI measurement \[mm\]
Time frame: Part A: during mechanical ventilation (up to 28 days)
Percentage pupil's variation
Pupil variation \[%\] during PPI measurement
Time frame: Part A: during mechanical ventilation (up to 28 days)
Maximal size variation
Maximal variation in pupil size \[mm\] during PPI measurment.
Time frame: Part A: during mechanical ventilation (up to 28 days)
Neuron-specific Enolase (NSE) [mcg/L]
NSE \[mcg/L\] in patients after cardiac arrest at 24, 48 and 72 hours
Time frame: Part A: From cardiac arrest until 72 hours after cardiac arrest
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