Critical Illness, Pain, Pain Management
Conditions
Keywords
Pain assessment, Pain management, Critical illness, mechanical ventilation, intensive care unit, Pupillary pain index
Brief summary
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.
Interventions
None listed
Sponsors
University of Zurich
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Part A * Admission to the intensive care unit * Adults (≥18 years) of all sex and gender * Mechanical ventilation Part B * Admission to the intensive care unit * Adults (≥18 years) of all sex and gender * mechanical ventilation * Continuous opioid therapy * Richmond Agitation Sedation Scale (RASS) ≤ -4 * Presumed duration of mechanical ventilation until the end of observations (until day 3) * Established vascular access suitable for blood sampling independent of study inclusion (arterial line or central venous catheter)
Exclusion criteria
Part A * None Part B * Previous enrolment into the current investigation * Tracheostomy * Chronic opioid use * Regional anaesthesia * Implanted pacemaker device * Allergy to silicone or ECG-electrodes * Ophthalmologic disease (e.g. ocular trauma, glaucoma) or past eye surgery * Fixed pupils * Known or suspected neurologic disease (including hypoxic encephalopathy) * Therapy with atropine or topical mydriatics in previous 24 hours or planned * Therapy with systemic steroids in previous 24 hours or planned * Therapy with neuromuscular blocking agents in previous 24 hours or planned * Stomatitis * Active oral or nasal bleeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Oral morphine equivalent (OME) per day of mechanical ventilation. | Part A: during mechanical ventilation (up to 28 days) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sufentanil dose per day of mechanical ventilation | Part A: during mechanical ventilation (up to 28 days) | average dose \[mcg/min\] |
| Opioid dose adjustments - Number of adjustments | Part A: during mechanical ventilation (up to 28 days) | Number of dose adjustments \[/hour\] and direction |
| Opioid dose adjustments - Relative change during pain assessment | Part A: during mechanical ventilation (up to 28 days) | Relative change of dose 45min after vs. 15min before ZOPA/PPI |
| Zurich Observational Pain Assessment (ZOPA) | Part A: during mechanical ventilation Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5 | 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. |
| Number of rescue analgesics administered per day | Part A: during mechanical ventilation (up to 28 days) | Bolus administration of opioids |
| Occurrence of adverse effects of pain per day of mechanical ventilation | Part A: during mechanical ventilation (up to 28 days) | * Intravenous antihypertensive treatment \[y/n\] * Atrial fibrillation \[y/n\] * anti-infective treatment \[y/n\] * Richmond Agitation Sedation Scale (RASS) \> +1 \[y/n\] |
| Number of sedatives used per day of mechanical ventilation | Part A: during mechanical ventilation (up to 28 days) | Average number of sedatives used in the intensive care unit (e.g. Propofol, Clonidine, Dexmedetomidine, Ketamine, Sevoflurane and Midazolam) |
| Richmond Agitation Sedation Scale (RASS) < -3 | Part A: during mechanical ventilation (up to 28 days) | 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 to extubation | 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. | Time to extubation from stop of analgosedation \[hours\] |
| Opioid prescription at ICU discharge | Part A: at ICU discharge assessed up to 5 days | \- Opioid prescription at ICU discharge \[y/n\] in patients discharged alive (as listed in the ICU discharge report) |
| Opioid prescription at hospital discharge | Part A: at hospital discharge assessed up to 10 days | \- Opioid prescription at hospital discharge \[y/n\] in patients discharged alive (as listed in the hospital discharge report) |
| Target nociception level | Part A: during mechanical ventilation (up to 28 days) | 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). |
| Opioid-free days in the ICU | Part A: from ICU admission to ICU discharge (up to 100 days) | Days free of opioid administration \[%\] |
| Pupillary Pain Index | - Part A: During mechanical ventilation - Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5 | 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). |
| Cortisol | Part B: day 2/visit 2, day 3/visit 4 | blood and saliva levels \[nmol/L\] |
| Amylase | Part B: day 2/visit 2, day 3/visit 4 | blood and saliva \[U/L\] |
| Critical Care Pain Observation Tool (CPOT) | Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5 | 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. |
| Subjective pain rating | Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5 | Questionnaire based rating of pain \[y/n\] by physician and nurses |
| Subjective rating of nociception level | Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5 | 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 |
| Trust in the Zurich Observational Pain Assessment (ZOPA) | Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5 | 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. |
| Trust in the Pupillary Pain Index (PPI) | Part B: day 2/visit 2, day 2/visit 3, day 3/visit 4, day 3/visit 5 | 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. |
| Pupil size before stimulation | Part A: during mechanical ventilation (up to 28 days) | Pupil size before stimulation PPI measurement \[mm\] |
| Percentage pupil's variation | Part A: during mechanical ventilation (up to 28 days) | Pupil variation \[%\] during PPI measurement |
| Maximal size variation | Part A: during mechanical ventilation (up to 28 days) | Maximal variation in pupil size \[mm\] during PPI measurment. |
| Neuron-specific Enolase (NSE) [mcg/L] | Part A: From cardiac arrest until 72 hours after cardiac arrest | NSE \[mcg/L\] in patients after cardiac arrest at 24, 48 and 72 hours |
Countries
Switzerland
Contacts
CONTACTSascha I David, Professor
CONTACTRolf Erlebach, MD
PRINCIPAL_INVESTIGATORRolf Erlebach, MD
University of Zurich
Outcome results
None listed