Adjunctive remifentanil infusion in deeply sedated and paralyzed ICU patients during fiberoptic bronchoscopy procedure: a prospective, randomized, controlled study
© Quintard et al.; licensee Springer. 2012
Received: 20 January 2012
Accepted: 4 June 2012
Published: 16 July 2012
Even with an adequate pain assessment, critically ill patients under sedation experience pain during procedures in the intensive care unit (ICU). We evaluated the effects of adjunctive administration of Remifentanil, a short-acting drug, in deeply sedated patient on variation of Bispectral Index (BIS) during a fiberoptic bronchoscopy.
A prospective, randomized, blinded, placebo-controlled study was conducted in 18-bed ICU. Patients needing a tracheal fibroscopy under deep sedation (midazolam (0.1 mg/kg per hour) fentanyl (4 μg/kg per hour)) and neuromuscular blocking (atracurium 0.5 mg/kg) were included in the study. A continuous monitoring of BIS, arterial pressure, and heart rate were realized before, during, and after the fiberoptic exam. An adjunctive continuous placebo or Remifentanil infusion was started just before the fiberoptic exam with a target effect-site concentration of 4 ng/ml using a Base Primea pump.
Mean arterial pressure and heart rates were comparable between the placebo and Remifentanil groups at all times of the procedure. We did not observe differences in the variation of BIS values between the two groups during procedure. We described no change in BIS values relative to the placebo group in this population.
In deeply sedated and paralyzed patients, receiving analgesic support based on a scale score an additional administration of short-acting analgesic drug, such as Remifentanil, seems not to be necessary for acute pain control.
KeywordsPain Intensive care Bispectral index Remifentanil
Pain, as it relates to care procedures, such as tracheal suction, mobilization, or wound care, is common in critically ill patients . As such, it may have a negative impact on patient comfort and can contribute to the development of posttraumatic stress disorder at intensive care discharge. The Behavioral Pain Scale (BPS), by evaluating facial expressions, upper limb movements, and compliance with mechanical ventilation, has been developed and validated to assess pain in mechanically ventilated, noncommunicating patients [2, 3]. Units that have implemented such pain monitoring procedures in daily patient care have reported decreases in hospital stays and in the number of ventilation days . Even in properly sedated patients, however, variations on BPS scores have been described during a short painful procedure . This suggests the need to optimize procedural pain control. Unfortunately in some situations, such as administration of muscle relaxants, this clinical scale cannot be used. Data indicate that variations of the Bispectral Index (BIS), initially developed to monitor the depth of anesthesia in the operating room, may be of interest to reflect cortical arousal associated with a painful procedure in mechanically ventilated, sedated, paralyzed patients .
Remifentanil, a short-acting opioid, is a particularly interesting option for the treatment of procedural pain in critically ill patients, due to its rapid onset and duration of action and metabolism independent of hepatic and renal status [7–9]. However, few data are available about its use in short painful procedure in ICUs .
The purpose of this study was to evaluate the effects of an adjunctive administration of Remifentanil on BIS variations during a short, painful procedure, such as fiberoptic bronchoscopy, in deeply sedated, paralyzed, mechanically ventilated patients.
All statistical analysis of data was performed by using StatView software. Results were calculated for groups of 20 patients, following a previous study , to obtain a 50 % decrease in the BIS value after tracheal suction in treated patients with a power of 80 % and α of 0.05. Results were expressed as mean (±SD), and all data were tested for normal distribution by the Kolmogorov-Smirnoff test. Differences between the pre-procedure and maximum BIS values for a given fiberoptic bronchoscopy were compared between the two groups by Student’s t test. BIS, heart rate (HR), invasive mean arterial pressure (MAP), SpO2, and CO2 for each time and changes of these parameters during the procedure were analyzed using an one-way (or two-way) ANOVA for repeated measures analysis.
Results and discussion
Demographic data (mean ± SD)
56 ± 18
51 ± 17
17 ± 12
15 ± 9
72 ± 29
78 ± 14
156 ± 54
175 ± 7
Length of sedation before fiberoptic act (days)
3 ± 2
4 ± 3
Median Midazolam dose before procedure (mg/h)
11 ± 3
13 ± 4
Median Fentanyl dose before procedure (μg/h)
150 ± 50
165 ± 45
Maximum BIS variation during procedure
15 ± 14
12 ± 10
Median total dose of Remifentanil during procedure(μg)
142 ± 95
155 ± 70
BIS monitoring (mean ± SD)
BIS value before fiberoptic bronchoscopy
36 ± 12
36 ± 11
Maximum BIS value during procedure
53 ± 8
54 ± 11
BIS value post fiberoptic bronchoscopy
42 ± 6
46 ± 9
We report in this study that adjunctive boluses of remifentanil are not necessary to prevent acute pain in deeply sedated patient.
Protocolized optimized sedation and pain control in the intensive care unit (ICU) can help to reduce duration of mechanical ventilation and length of stay in ICU and hospital by reducing drug consumption [4, 19]. However, it could be not sufficient to provide an adequate analgesia during an acute painful care. Indeed, Payen et al. described a rising of BPS during procedure in patient under correct level of sedation . Optimization of analgesic control, by adjunctive therapy for example, could be needed to impair the risk of posttraumatic stress. Remifentanil, because of its pharmacologic properties could be a very interesting approach. This short-acting drug could protect the patient during procedure without increasing the risk of oversedation and consequences. In this study, we did not observe differences in the variation of BIS values, as a surrogate for analgesia evaluation, between the Remifentanil and placebo groups in mechanically ventilated, deeply sedated patients during a fiberoptic bronchoscopy. Moreover, BIS value did not change over time in both groups. We also do not observe significant difference between placebo and Remifentanil group according to PAM and heart rate. Heart rate is always higher in the placebo group than in the remifentanil one, which could be explained by direct chronotropic negative effect of Remifentanil. The absence of BIS variation observed during the procedure could be explained by different ways. The very low values recorded at the beginning of the procedure can limit the impact of adjunctive therapy. Indeed, we choose to study a particular group of patients needing deep sedation for procedure. We may hypothesize that deep sedation conducted to low initial BIS value, leading to blunt significant variation in BIS value. Statistically, an expected decrease in BIS value of 50 %, used in anterior studies, is probably overestimated in this particular setting of deep sedated patients, and the sample size could be underevaluated. Tolerance to fentanyl developed before the procedure could limit the interpretation of results, but length of sedation before procedure was short and dose was controlled by pain scale. Furthermore, no signs of opioids tolerance were developed by patients. We can also hypothesize that the level of pain is not sufficient but previous study described fiberoptic examination as one of the most painful procedure . Remifentanil doses could not be enough efficient, but the absence of BIS variation in the placebo group is not in accordance with this hypothesis.
In particular, critically ill conditions, such as patients with brain trauma or respiratory failure, or for care procedure (fiberoptic bronchoscopy, tracheotomy…), neuromuscular blocking agents administration is recommended making the use of sedation scale scores, such as the Behavioral Pain Scale (BPS) , impossible. Bispectral Index, developed initially to monitor depth of anesthesia in the operating room [13, 20, 21], could be an approach. In an experimental study of healthy volunteers, adjunctive opioids to volatile agents-based anesthesia increases clinical sedation but has no impact on BIS value. However, patients did not suffer from acute painful procedure . In ICU, BIS use remains controversial because of the high level of variability of this parameter as described in our study (Figure 4), which led us to study the variation of this rather isolated value. Some authors have concluded that the most recent version of BIS—BIS XP—is useful in the ICU setting for assessing sedation , whereas others do not share this view . The use of BIS monitoring to assess pain in our study could be criticized, but it was shown to be sensitive to nociceptive stimuli in critically ill, sedated patients [6, 25]. Brocas et al. were able to blunt BIS variations by adding a bolus of a short-acting opioid to sedated patients before endotracheal suction. Other studies have described similar results with other opioids . In accordance with these results, and with the proposition of French consensus on sedation in the ICU, we decided to use this device to evaluate the level of pain of our critically ill patients .
Our study shows that in deeply sedated patients receiving analgesic support based on a scale score, additional administration of short-acting analgesic drug, such as Remifentanil, does not seems to be necessary for acute pain control assessed by BIS variation. These data should be studied further in a population of patients who need less sedation.
A.1. Riker sedation-agitation scale (SAS)
A.1.1. Score term descriptor
Dangerous Agitation Pulling at ET tube, trying to remove catheters, climbing over bedrail, striking at staff, thrashing side-to-side
Very Agitated Requiring restraint and frequent verbal reminding of limits, biting ETT
Agitated Anxious or physically agitated, calms to verbal instructions
Calm and Cooperative Calm, easily arousable, follows commands
Sedated Difficult to arouse but awakens to verbal stimuli or gentle shaking, follows simple commands but drifts off again
Very Sedated Arouses to physical stimuli but does not communicate or follow commands, may move spontaneously
Unarousable Minimal or no response to noxious stimuli, does not communicate or follow commands
Sedation agitation scale
Behavioral pain scale
No financial support.
Conflicts of interest: none of the authors has any conflict of interest.
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