Received: 28 June 2001Accepted: 21 November 2001Published online: 12 January 2002©Springer-Verlag 2002
To evaluate theimpact of an alfentanil dose on bi-spectral index (BIS) variations dur-ing tracheal suction in ICU sedatedpatients.
 Design and setting:
A pro-spective open-label pilot study in a12-bed surgical ICU in a university-affiliated, tertiary referral hospital.
: Eleven sedated (midazolamplus fentanyl) mechanically ventilat-ed patients.
Continu-ous monitoring of BIS with arterialpressure and heart rate before, dur-ing, and after tracheal suction with-out (control period) and with an in-travenous bolus of alfentanil(15µg/kg, alfentanil period) beforesuction.
Steady-state BISvalue was 61±8 for the control periodand 59±7 for the alfentanil period.Blood pressure and heart rate weresimilar between baseline periods. Oneminute after tracheal suction, a sig-nificant increase in BIS level wasobserved in the control period,which remained significantly differ-ent from the alfentanil period until10min later. Significant higher sys-tolic and diastolic blood pressure andheart rate were observed during thecontrol period than the alfentanil pe-riod. However, no difference inRamsay scores was observed betweenthe two periods.
: Analfentanil bolus of 15µg/kg markedlyreduced the increase in BIS values,blood pressure, and heart rate ob-served immediately after trachealsuction. Therefore BIS monitoring inICU may help to improve analgesiaduring invasive events.
Bispectral index · Sedation · Alfentanil · Ramsay score ·Tracheal suction · Intensive care unit
Intensive Care Med (2002) 28:211–213DOI 10.1007/s00134-001-1189-y
Elsa BrocasHervé DupontCatherine Paugam-BurtzFrédérique ServinJean MantzJean-Marie Desmonts
Bispectral index variations during trachealsuction in mechanically ventilated critically ill patients: effect of an alfentanil bolus
Ensuring adequate sedation and analgesia is an importantgoal of care of critically ill patients. However, definitionand maintenance of “adequate” sedation remain difficult[1]. Of the various sedation scales reported the Ramsayscore is the most widely used [2]. Although the Ramsayscore may be helpful in detecting oversedation, it doesnot measure or anticipate pain at all. The analogue visualscale usually used for evaluating pain in the postopera-tive period is often ineffective in critically ill patients.Nociceptive stimuli are frequently encountered in theroutine care of ICU patients, such as nursing, trachealsuction, physiotherapy, and any mobilization [3]. Objec-tive tools to assess the impact of these stimuli on awak-eness or analgesia of critically ill patients are scarce.Electroencephalography (EEG) using the bispectralindex (BIS) has recently been developed to monitordepth of anesthesia [4]. BIS is expressed as a value rang-ing from 0 (plate EEG) to 100 (awake patient). The levelof BIS seems to be correlated with the level of hypnosis[4] but not to analgesia. However, clinical studies onboth volunteers [5] and anesthetized [6] patients haveshown that pain stimulation results in an increase in BISlevel if the level of analgesia is weak. Recent investiga-tions have evaluated the value of monitoring sedation inICU [7, 8]. BIS monitoring could be sensitive to the no-ciceptive stimuli experienced by critically ill patients.
E. Brocas · H. Dupont (
) C. Paugam-Burtz · F. Servin · J. Mantz J.-M. DesmontsDepartment of Anesthesiology and Surgical ICU, University of Paris 7,Bichat-Claude Bernard Hospital, 46 Rue Henri Huchard, 75877 Paris Cedex 18, France e-mail: +33-1-40258118Fax: +33-1-40258869
The aim of the present study was to evaluate the effect of an intravenous bolus of alfentanil on the variations inBIS level associated with tracheal suction, a stimulus of-ten reported as particularly painful by critically ill pa-tients [3].
Patients and methods
Eleven patients hospitalized in a 12-bed tertiary university surgi-cal ICU were included in a prospective pilot study (August1999–February 2000). The inclusion criterion was mechanicalventilation with intravenous sedation. Exclusion criteria were: (a)renal failure (creatinine clearance <50ml/min), (b) liver failure(prothrombin time <30% or hepatic encephalopathy), (c) intracra-nial evolving disease (brain injury, brain tumor, abscess, stroke, orhemorrhage), and (d) patients paralyzed for any reason. The pa-tients comprised eight men and three women, with median age66years (range 43–79), weight 72kg (50–99), height 1.75m(1.55–1.8), and Simplified Acute Physiology Score 44 (24–64).The MacCabe score was “not fatal” in six patients and “fatal in thenext 5years” in five. The diagnoses on admission were septicshock (
=3), peritonitis (
=2), acute pancreatitis (
=2), and others(
=4).The sedation protocol was the same for all the patients. Thisconsisted of intravenous midazolam (0.1mg/kg per hour) and fen-tanyl (4µg/kg per hour). The median hourly sedative dose of mid-azolam was0.07mg/kg (0.04–0.16) and that of fentanyl 2.9µg/kg(1.9–9.7) For the second measurement median alfentanil dose was14µg/kg (11–20). Six patients underwent treatment with epineph-rine or norepinephrine during the study. The level of sedation wasclinically assessed by the Ramsay score, and infusion rates wereadjusted to obtain a Ramsay score at 4 or 5 and a BIS level at 60before the beginning of the protocol. We chose this value becauseBIS values of 40–65 have been suggested for deep sedation [4] asneeded for controlled mechanical ventilation. BIS recording wascontinuous during the entire study period with an Aspect A-1000monitor (Aspect Medical System, USA; BIS version 3.03). Fourelectrodes in a bifrontal schema (F7-Fz; F8-Fz) were used. Theimpedance of each electrode was checked and maintained below5000
to ensure a good quality of the signal. Patients’ demo-graphic characteristics„ severity score (Simplified Acute Physiolo-gy Score II, MacCabe score), and the main diagnosis on admissionwere recorded.Each patient served as his own control. The baseline level of BIS before stimulation was recorded during 10min; then the tra-chea was suctioned twice for 30s. Mean baseline BIS was 60±8,without any difference between control and alfentanil for any pa-tient. The BIS level was recorded continuously during the proce-dure until 15min after cessation of suction. Fifteen minutes afterBIS level returned to baseline an intravenous bolus of alfentanil(15µg/kg) was administrated 2min (
) before tracheal suction),and the measurement was performed again. For each record of BIS level, systolic (SBP) and diastolic blood pressure (DBP) andheart rate (HR) were noted. Moreover, Ramsay score was evaluat-ed 10 and 5min before t
, at t
, and 5, 10, and 15min after t
.Results are expressed as median with extremes for populationdata and mean with standard deviation for BIS level, HR (bpm)and SBP and DBP (mmHg). Values during the control period werecompared to those during the alfentanil period using the nonpara-metric paired signed test. The
test was used to compare qualita-tive data with Yates’ correction or Fisher’s exact test, if needed. A
value less than 0.05 was considered significant.
BIS variations during the protocol are presented inFig.1. Immediately after tracheal suction (integratingtime=30s), BIS values were significantly higher duringthe control period than the alfentanil period (88±14 vs.65±9,
=0.02). This difference remained significant10min after suction. The pattern of individual variationsin BIS according to the period was the same (data notshown). The Ramsay score was 4 or 5 in all patients,without change at any time of the study, even during tra-cheal suction. The relationship between the Ramsayscore observed and the level of BIS is exposed in Fig.2.No change in the quality of the BIS signal was observed.No patient experienced major coughing during suction.No variation in oxygen saturation was observed. Duringtracheal suction SBP, DBP, and HR were significantlyhigher in the control period than after alfentanil bolus: 122±19 vs. 105±20mmHg (
=0.02), 65±11 vs.58±11mmHg (
=0.03), and 100±20 vs. 95±19bpm(
=0.04). No modification in HR, SBP, and DBP, or BISvalues was observed between the bolus of alfentanil andthe beginning of the tracheal suction.
Comparison of the BIS values (mean ±SD) between thecontrol group and the group receiving an intravenous bolus of alf-entanil before tracheal suction according to the protocol.
Bi-spectral index. *
<0.05 between groups
Comparison between the BIS values (mean ±SD) and theRamsay score during tracheal suction according to the group re-ceiving or not alfentanil 2min before.
Bispectral index.*
<0.05 between groups
This study is the first to demonstrate BIS variations during tracheal suction in critically ill patients. Thesevariations were blunted by the administration of an alf-entanil bolus before tracheal suction. Together, these re-sults suggest that BIS is sensitive to nociceptive stimuliin critically ill patients.There are some limitations to our study. First, few pa-tients (
=11) were enrolled, but the size of the sampleenabled us to show a statistical difference for the prima-ry end-point (BIS values). Second, each patient was hisown control, and a cross-over study was not performed.We did not use randomized control vs. alfentanil periodsto avoid a possible persistent effect of alfentanil duringthe control period if it had been administrated first. Also,a pharmacokinetic/pharmacodynamic simulation wasperformed before the beginning of the study using Stan-pump software. This showed that a period of 2h was re-quired for alfentanil to be cleared from its site of actionin the brain after a bolus of 15µg/kg. Maintaining hemo-dynamic and respiratory stability for 2h is often verydifficult in severe ICU patients. Instead of increasing therate of fentanyl infusion the administration of alfentanilwas been chosen owing to its rapid onset of action(threefold faster than fentanyl).During the control period tracheal suction was rapid-ly followed by an increase in BIS values This is mostlikely to be due to a stimulation of central noradrenergicneurons that could realize a kind of “cortical awaken-ess” [9]. This is supported by the concomitant increasein HR and blood pressure, which reflects adrenergic hy-peractivation. This cortical arousal has recently been in-vestigated during tracheal suction in critically ill pa-tients with median nerve somatosensory evoked re-sponses [10]. Therefore it may be suggested that BIS re-flects not only the level of hypnosis but also the level of pain. However, the difference between pain-inducedcortical arousal or cortical arousal alone without pain isslight. Interestingly, no relationship was found betweenBIS values and the sedation level assessed by Ramsayscore. This apparent discrepancy could be explained bysome limitations in sensitivity and specificity of BIS it-self [11]. Also, data obtained from a large database of anesthetized patients may not always apply to sedatedcritically ills [11]. More likely, the Ramsay score mea-sures the depth of sedation but is not sensitive to noci-ceptive stimuli [2]. Therefore it may not exhibit a goodsensitivity to tracheal suction, which is a nociceptivestimulus. Finally, in the present study a Ramsay score of 4 or 5 reflecting deep hypnosis corresponds to BIS val-ues of 60. Although some reports suggest that BIS val-ues and sedation scores may be correlated, our data donot support these findings [7, 8].In conclusion, this prospective pilot study suggeststhat BIS variations reflect cortical reactivity to trachealsuction in critically ill sedated and ventilated patients.BIS monitoring in ICU may help to optimize analgesiaduring invasive events, but this remains to be validatedin controlled trials.
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