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Assessment of pain in critically ill children. Is cutaneous conductance a reliable tool?
Journal of Critical Care 30 (2015) 481–485
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Assessment of pain in critically ill children. Is cutaneous conductance a reliable tool?☆ M.J. Solana, MD, PhD a,b,⁎, J. Lopez-Herce, MD, PhD a,b, S. Fernandez, MD a,b, R. Gonzalez, MD a,b, J. Urbano, MD, PhD a,b, J. Lopez, MD a,b, J.M. Bellon, PhD b a b
Pediatric Intensive Care Service, Hospital General Universitario Gregorio Marañón, Dr Castelo 47, 28009 Madrid, Spain Instituto de Investigación del Hospital Gregorio Marañón, Doctor Esquerdo 46, 28009 Madrid, Spain
a r t i c l e
i n f o
Keywords: Pain Children Skin conductance Sedation Monitoring Critical care
a b s t r a c t Purpose: The purpose of this study is to assess the usefulness and accuracy of skin conductance (SC) as a tool to evaluate the level of sedation and pain in pediatric critical patients during painful procedures and to compare it with hemodynamic variables, clinical scales, and bispectral index (BIS). Materials and methods: This is a prospective observational study in 61 critical children undergoing invasive procedures. Hemodynamic data (heart rate and arterial blood pressure), clinical scales punctuation (Ramsay, COMFORT, and numeric rating pain scales), BIS, and the number of fluctuations of SC per second were collected before, during, and at the end of the procedure. Results: The mean age of the patients was 42.9 (range, 1 month to 16 years). Seventy-two point six percent were postcardiac surgery patients. Nonmuscle-relaxed patients showed a moderate increase in heart rate (P = .02), numeric rating pain scales (P = .03), and Ramsay scale (P = .002). The number of fluctuations of SC per second increased significantly during the procedure (basal, 0.1; maneuver, 0.2; P = .015), but it never reached the level considered as pain or stress nor did it precede clinical scales or BIS. None of the variables studied showed a significant change during the procedure in muscle-relaxed patients. Conclusions: Skin conductance was not found to be more sensitive or faster than clinical scales for the assessment of pain or stress in critical children undergoing painful procedures. Skin conductance was not useful in musclerelaxed children. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Children admitted to a pediatric intensive care unit are commonly subjected to painful procedures and stressful situations that require the administration of sedative and/or analgesic drugs [1]. The management of sedation in these patients is difficult because sedative drugs have a narrow therapeutic window, and patients frequently have altered mechanisms of hepatic and renal clearance and because critically ill children cannot adequately verbalize the intensity and site of pain and have more tolerance and physical dependence than adults [2]. Anatomic and neurochemic pathways for the transmission of pain are developed at birth, and children can respond to it with physiologic, metabolic, hormonal, and behavioral changes. Pain causes hemodynamic instability, hypoxemia, and it increases intracranial ☆ This study was funded by a scholarship of the Madrid and Castilla La Mancha Pediatric Society, Madrid, Spain. ⁎ Corresponding author. Servicio de Cuidados Intensivos Pediátricos Hospital General Universitario Gregorio Marañón Dr Castelo 47 28009 Madrid, Spain. Tel.: + 34 915290327; fax: +34 915868018. E-mail addresses: [email protected] (M.J. Solana), [email protected] (J. Lopez-Herce), [email protected] (S. Fernandez), [email protected] (R. Gonzalez), pazienziainfi[email protected] (J. Urbano), [email protected] (J. Lopez), [email protected] (J.M. Bellon). http://dx.doi.org/10.1016/j.jcrc.2015.01.008 0883-9441/© 2015 Elsevier Inc. All rights reserved.
pressure. On the other hand, excessive sedation can cause cardiac and respiratory depression, an increase in the duration of mechanical ventilation and abstinence syndrome [3,4]. Continuous monitoring of the level of sedation or pain in critically ill children is imperative during painful procedures, to find the right balance between being without discomfort and not being oversedated [5]. Several methods have been used for the evaluation of the level of sedation in critical patients, although no criterion standard exists [3,6]. Hemodynamic variables, clinical scales, and analysis of the electroencephalogram 1(EEG) are the most widely used methods [2]. However, these methods have some limitations. Hemodynamic parameters are influenced by the volemic status of the patient, drugs, and the autonomous nervous system [7,8]. Sedation scales are subjective methods and cannot be applied in profoundly sedated or musclerelaxed patients [6,9] In the last years, new methods based on the analysis of the EEG have been developed. Bispectral index (BIS) is a noninvasive method that assesses the level of consciousness of the patient by analyzing the frequencies of the EEG waves. Although it has been proven to be a useful 1 EEG: electroencephalogram; 2 BIS: biespectral index;3 NFSC: number of fluctuations of skin conductance per second; 4 SRPS: Faces Pain Scale-revised; 5HR: heart rate; 6SBP: systolic blood pressure; 7DBP: diastolic blood pressure; 8RR: respiratory rate.
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method in critical patients, it also has some limitations: several clinical conditions and electronic devices like pacemakers could induce artifact signal pollution [2,10-13]. Skin conductance (SC) is a noninvasive method for the evaluation of pain or stress [5,14,15]. Pain or stress produces an increase in subcortical and cortical activity, which generates a sympathetic download that releases acetylcholine that acts on the muscharinic receptors, which stimulate sweat gland secretion, resulting in changes in SC [14]. The peak of the SC appears 1 to 2 seconds after a stimulus and is, in theory, independent of temperature, muscle relaxation, sympathomimetic drugs, or changes in the volume status of the patient. Skin conductance seems to be useful for monitoring the level of sedation or pain in preterms and infants [16,17], postsurgical patients [18], children with minor injuries [19], with mechanical ventilation [5], and critically ill adult patients [20]. However, there are few data related to the usefulness of this device in critically ill children [5], and there is not much experience in muscle-relaxed patients. The purposes of this study were to evaluate the usefulness and accuracy of this device for the assessment of the level of sedation and analgesia during painful procedures in a pediatric critical care unit; to compare this method with hemodynamic variables, clinical scales, and BIS during painful procedures; and, finally, to determine the usefulness of SC in pediatric muscle-relaxed patients. 2. Material and methods 2.1. Participants We conducted a prospective, observational study, which included critically ill children aged from 1 month to 16 years undergoing a painful technique. Painful procedures included arterial or central venous line catheter insertion, urinary tract catheterization, insertion of a nasogastric tube, tracheal aspiration, pleural catheter removal, left atrial pressure catheter removal, lumbar puncture, or sternal closure. Approval was obtained from the institutional review boards of the hospital, and informed consent was obtained from the parent or legal guardian of each child enrolled. Patients were excluded if they were being treated with anticholinergic drugs (high-dose atropine or neostigmine) or sympathetic central nervous system inhibitors (ie, clonidine), if they had a peacemaker or defibrillator, or if they rejected to participate in the study. 2.2. Test methods After being included in the study, a BIS XP 3.4 monitor (Aspect Medical Systems, Newton, MA) was settled. Frontal sensors with 3 ZIP Prep pediatric electrodes in children younger than 1 year and Quatro ZIP Prep electrodes in children older than 1 year were used. The BIS monitor was connected to a Philips Intellivue MP70 monitor. Skin conductance was analyzed by a Med-Storm monitor (MedStorm Innovation AS, Oslo, Norway). This device measure real-time changes in SC due to pain or stress by analyzing the peaks or number of fluctuations of SC per second (NFSC) and the relative area under the curve [21]. An NFSC peak is defined as minimum followed by a maximum in conductance values Micro Siemens (μS) [5,21]. The system can measure conductance values in the range of 1 to 200 μS, with a noise level below 0.002 μS and has error detection that provides a warning about electrode looses or external interferences [21]. An applied voltage of 50 mV and a 3-electrode system (Sensormedics, CA, Oslo, Norway) were used. The 3-electrode system comprised a measuring electrode (M), a countercurrent electrode (C), and a reference voltage electrode (R), which ensured a constant applied voltage across the stratum corneum. The electrodes were settled on the soles in children younger than 1 year and on the palms in older children to improve the quality of the signal, as older children have a thicker sole corneal stratum than infants.
The electrodes were placed according to the Edelberg guidelines for the placement of electrodes to obtain the most sensitive measurement [14]. According to the specifications of the manufacturer, a value greater than 0.21 peaks per second was considered to be as pain or discomfort. 2.2.1. Clinical scales Anxiety and pain were measured by the Modified Ramsay scale, COMFORT scale, and self-report pain scale (SRPS) (Faces Pain ScaleRevised in infants and children after receiving sedatives and color rating scale for conscious children). Modified Ramsay scale is an 8-point scoring system, which quantifies the level of sedation [22] and has been used to evaluate the level of sedation during the performance of procedures in critically ill adults and children [2,3,6,22]. This scale is scored from 1 (patient anxious and agitated or restless or both) to 8 (no response to any stimulus including pain). The COMFORT scale is a useful score to measure the levels of stress in critically ill children requiring mechanical ventilation [23]. It evaluates 8 parameters, scoring between 1 and 5 points each. 2.3. Protocol Previous to the procedure, heart rate (HR [beats per minute]), systolic (SBP [millimeter of mercury]) and diastolic arterial blood pressure (DBP [millimeter of mercury]), and respiratory rate (breaths per minute) were recorded as well as the punctuation in clinical scales, BIS, and NFSC. All these measures were repeated during the procedure and 5 minutes after the procedure. Maximum registered values of the procedure were recorded and considered for analysis. The basal pharmacologic sedation-analgesia treatment (type and dosage) of the patient as well as the additional doses needed to achieve a good level of analgesia was also recorded. The administration of additional doses was at the discretion of the attending physician based on the clinical status of the patient. 2.4. Statistical methods Data were analyzed with SPSS software version 18.0. The evolution of hemodynamic parameters, clinical scales, BIS, and NFSC were analyzed using the Wilcoxon test. Correlation between variables was estimated using the Spearman rank correlation coefficient (ρ). 3. Results Sixty-one patients were included in the study. The mean age was 42.9 ± 56.5 months. Children were diagnosed as postcardiac surgery in 72.6%, respiratory failure in 9.7%, neurologic disease in 6.5%, oncology patients in 6.5%, sepsis in 3.2%, and others in 1.6%. The most common procedure was pleural or atrial left pressure catheter removal (37.7%), followed by arterial or venous canalization (27.8%), tracheal tube aspiration (18%), nasogastric or urinary tract tube insertion (9.8%), lumbar puncture (4.9%), and chest closure in a cardiac patient (1.6%). Continuous midazolam infusion was used in 42% of patients (mean dose, 1.5 ± 2.4 μg/kg per minute), fentanyl infusion in 61% (mean dose, 1.0 ± 1.2 μg/kg per hour), remifentanil infusion in 6% (mean dose, 0.05 ± 0.2 μg/kg per minute), and propofol infusion in 22% of patients (mean dose, 0.6 ± 1.3 mg/kg per hour). Fifteen patients received continuous muscle relaxation with vecuronium (mean dose, 0.13 ± 0.1 mg/kg per hour). 3.1. Evolution of hemodynamic parameters, clinical scales, BIS, and NFSC variables The evolution of hemodynamics, clinical scales, BIS, and NFSC in basal situation, during the procedure and at the end of the procedure is registered in Table 1. The NFSC evolution is represented in Figure 1.
MJ. Solana et al. / Journal of Critical Care 30 (2015) 481–485 Table 1 Evolution of the hemodynamic, clinical scales, BIS, and NFSC values
HR (beats per minute)a SBP (mm Hg) DBP (mm Hg) Ramsay COMFORT NRS (FNR, CNR) BIS NFSC
Basal
Maneuver
Final
Mean, SD
Mean, SD
Mean, SD
127.6 (29.05) 99.7 (17.2) 56.4 (15) 4.6 (2.8) 19 (6.9) 2.9 (2.7) 69.7 (24.4) 0.09 (0.17)
132.8 (21) 98.4 (20.2) 56.7 (14.9) 5.7 (2.2) 18.2 (5.8) 3.9 (2.8) 67.4 (24.4) 0.14 (0.18)
131.2 (22.3) 96.4 (20.3) 53.7 (12.2) 5.2 (2.4) 17.7 (5.7) 2.6 (2.3) 68.1 (24.4) 0.6 (0.1)
P, basal maneuver .019 .425 .763 .020 .252 .039 .504 .017
NRS indicates numeric rating scale; FNR, faces rating scale; CNR, color rating scale; HR(bpm), heart rate (beats per minute); SBP, systolic blood pressure; DBP, diastolic blood pressure; NRS, numeric rating scale, FNR, faces rating scale; CNR, color rating scale; BIS, biespectral index; NFCS, number of fluctuations of skin conductance. a Heart rate (beats per minute).
During the procedure, the NFSC and the SRPS scale increased in 25 patients (41%), the COMFORT scale increased in 10 (18%), BIS increased in 19 children (40%), and the Ramsay scale decreased in 8 patients (13%). A statistically significant increase in HR, Ramsay, and SRPS scales and the NFSC between the baseline situation and the procedure were observed. No significant changes were observed in the remaining analyzed parameters (Table 1).
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Table 2 Evolution of the hemodynamic, clinical scales, BIS, and conductance values in nonmusclerelaxed and muscle-relaxed patientsa Basal
Maneuver
Final
P⁎
Mean, SD
Mean, SD
Mean, SD
Basal maneuver
132.4 (18.6) 100 (2.1) 59.4 (14.4) 5.1 (2.1) 20.3 (5.2) 4.8 (2.6) 78.8 (18.2) 0.2 (1.6)
130.4 (20.7) 97.8 (19.6) 55.5 (11.9) 4.5 (2.2) 19.5 (5.1) 3.2 (2.3) 79.5 (19.5) 0.1 (0.8)
.026 .191 .846 .002 .514 .037 .28 .015
136.1 (22.1) 95.3 (18.7) 49.6 (12.9) 7.7 (1) 12.4 (3) 1.2 (1.4) 40.8 (15.1) 0.02 (0.05)
133.5 (27.7) 92 (22.3) 48.1 (11.9) 7.2 (1.5) 12.2 (2.8) 1.3 (1.5) 44.5 (10.5) 0 (0)
.64 .227 .385 1 .514 .655 .271 .785
Nonmuscle-relaxed patients HR (beats per minute) 127.5 (29.4) SBP (mm Hg) 100.2 (17.2) DBP (mm Hg) 58.6 (15) Ramsay 3.6 (2.4) COMFORT 21.5 (6.5) NRS (FNR, CNR) 3.5 (2.8) BIS 78.8 (21.6) NFSC 0.1 (1.5) Muscle-relaxed patients HR (beats per minute) 128.7 (26.9) SBP (mm Hg) 99.2 (18.4) DBP (mm Hg) 50.9 (12.1) Ramsay 7.7 (1) COMFORT 12.4 (3) NRS (FNR, CNR) 1.3 (1.6) BIS 47.2 (12.3) NFSC 0.02 (0.04)
SBP, systolic blood pressure; DBP, diastolic blood pressure; NRS, numeric rating scale, FNR, faces rating scale; CNR, color rating scale; BIS, biespectral index; NFCS, number of fluctuations of skin conductance. ⁎ Statistically significant p b 0.05. a Heart rate (beats per minute).
3.2. Comparison between muscle-relaxed and nonmuscle-relaxed patients The evolution of hemodynamic parameters, clinical scales, BIS, and NFSC in basal situation and during the procedure in muscle-relaxed and nonmuscle-relaxed patients is registered in Table 2. The NFSC, Ramsay, and SRPS scales increased significantly during the procedure in the nonmuscle-relaxed group. None of the parameters presented significant changes in the muscle-relaxed group during the procedure. Only 3 of the muscle-relaxed patients showed changes in the NFSC, but they were not significant. Two of these patients had a slight increase in the NFSC, and the third one presented a decrease in the NFSC that coincided with a drop in BIS punctuation.
vs 1 ± 1.3 μg/kg per hour; remifentanil, 0.1 ± 0.3 vs 0 μg/kg per minute; propofol, 0.6 ± 1.4 vs 0.6 ± 1.3 mg/kg per hour). The evolution of hemodynamic parameters, BIS, clinical scales, and NFSC between both groups of age is reflected in Table 3. Children younger than 12 months showed significant changes in the HR and Ramsay score during the procedure, whereas children older than 12 months presented significant changes in the systolic and diastolic blood pressure, the clinical scales, and the NFSC. None of the groups of age showed significant differences in the BIS value during the procedure.
3.3. Evolution of the variables according to age
3.4. Evolution of variables according to diagnosis
Twenty-seven patients were younger than 12 months. Forty point seven percent of the children younger than 12 months and 12% of the children 12 months or older were muscle-relaxed, although no significant differences in the dosage of sedation existed between both groups (midazolam, 1.8 ± 2.3 vs 1.3 ± 2.5 μg/kg per minute; fentanyl, 1.1 ± 1.3
Patients were divided into 2 groups regarding diagnosis: postoperatory cardiac patients and other diagnosis (Table 4). Cardiac patients showed significant changes in HR, Ramsay and SRPS scales, and NFSC during the procedure, whereas noncardiac patients showed significant changes only in diastolic pressure during the maneuver.
Figure 1. Evolution of the NFSC in total population and in muscle and nonmuscle-relaxed patients.
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Table 3 Evolution of the hemodynamic, clinical scales, BIS and NPPS values in children younger than 12 months and children 12 months or oldera
Children b12 mo HR (beats per minute) SBP (mm Hg) DBP (mm Hg) Ramsay COMFORT NRS (FNR, CNR) BIS NFSC Children ≥12 mo HR (beats per minute) SBP (mm Hg) DBP (mm Hg) Ramsay COMFORT NRS (FNR, CNR) BIS NFSC
Basal
Maneuver
Final
P⁎
Basal
Maneuver
Final
P⁎
Mean, SD
Mean, SD
Mean, SD
Basal maneuver
Mean, SD
Mean, SD
Mean, SD
Basal maneuver
136.3 (20.9) 95.4 (16.9) 54.4 (11.6) 4.7 (2.9) 19.2 (7.8) 3.2 (3.1) 68.2 (24.8) 0.12 (1.1)
139.2 (16) 90.2 (15.7) 52.4 (11.4) 5.8 (2.1) 16.7 (4.7) 3.03 (2.4) 61.9 (25.4) 0.17 (1.3)
136.8 (18.1) 88.6 (19.3) 50.3 (10.6) 2.4 (2.7) 16.4 (4.7) 2.7 (2.2) 63.5 (20.3) 0.09 (0.6)
.027 .327 .871 .012 .161 .682 .413 .529
125.7 (16.8) 98.3 (15.3) 57.5 (18.9) 6.1 (3.3) 17.6 (10.4) 2.7 (3.6) 53.9 (26.7) 0.2 (0.3)
120.8 (22.2) 88.8 (10.8) 49.3 (9.9) 2.1 (2.9) 16.8 (9.6) 2.1 (2.9) 54.6 (22.4) 0.1 (0.2)
.122 .003 .011 1 .443 .18 .544 .042
120.2 (32.7) 103.7 (17.2) 58.9 (16.8) 4.4 (2.7) 19.3 (6.5) 2.7 (2.4) 71.3 (23.8) 0.06 (0.6)
127.8 (20.7) 106.3 (21.6) 61.3 (16) 5.6 (2.3) 19.6 (6.4) 4.7 (3) 73.4 (22.7) 0.1 (0.6)
126.3 (25) 103 (19.4) 56.9 (12.9) 5.2 (2.2) 18.6 (6.3) 2.8 (2.4) 74.8 (23.2) 0.04 (0.3)
.306 .004 .05 .047 .066 .02 .109 .003
135 (16.2) 98.1 (22.4) 55.9 (14.8) 5.9 (1.1) 17.4 (3.3) 4.1 (2.8) 66.3 (23.3) 0.1 (0.1)
134.3 (20.3) 103.3 (24.5) 56.1 (12.5) 5.8 (2.2) 16.8 (4) 2.8 (2.3) 67.1 (18.8) 0 (0.1)
.699 .123 .935 .495 .439 .091 .98 .039
133.7 (20.2) 97.7 (22.4) 54.7 (11.7) 5.3 (2) 19.2 (4.4) 4.3 (2.5) 79.9 (17.4) 0.1 (0.2)
132.2 (20.3) 93.9 (20.4) 52.5 (12.4) 4.1 (1.9) 19.1 (4.1) 3 (1.9) 80.7 (15.9) 0.1 (0.2)
.502 .161 .565 .001 .013 .476 .949 .465
SBP, systolic blood pressure; DBP, diastolic blood pressure; NRS, numeric rating scale, FNR, faces rating scale; CNR, color rating scale; BIS, biespectral index; NFCS, number of fluctuations of skin conductance. ⁎ Statistically significant p b 0.05. a Heart rate (beats per minute).
None of the 2 groups presented significant changes in the BIS or in the COMFORT punctuation.
Traqueal aspiration HR (beats per minute) 119.2 (21.5) SBP (mm Hg) 101.3 (13.3) DBP (mm Hg) 59.3 (20.6) Ramsay 6.1 (3.3) COMFORT 16 (8.6) NRS (FNR, CNR) 1.7 (2.5) BIS 59.3 (22.1) NFSC 0.1 (0.1) Catheter insertion HR (beats per minute) 131.3 (21.5) SBP (mm Hg) 97.9 (21.1) DBP (mm Hg) 56.6 (14.9) Ramsay 5.4 (2.7) COMFORT 18.4 (5.4) NRS (FNR, CNR) 2.5 (2) BIS 66.9 (23.4) NFSC 0 (0) Pleural catheter insertion/removal HR (beats per minute) 130.1 (35.4) SBP (mm Hg) 98.5 (16.1) DBP (mm Hg) 54.1 (11.6) Ramsay 3 (2) COMFORT 22.5 (6.7) NRS (FNR, CNR) 3.7 (3) BIS 81.2 (20.8) NFSC 0.1 (0.2)
HR(bpm), heart rate (beats per minute); SBP, systolic blood pressure; DBP, diastolic blood pressure; NRS, numeric rating scale, FNR, faces rating scale; CNR, color rating scale; BIS, biespectral index; NFCS, number of fluctuations of skin conductance. ⁎ Statistically significant p b 0.05.
3.5. Evolution of variables according to the technique Patients were divided into 3 groups according to the technique: endotracheal aspiration, central and peripheral line insertion, and catheter/drainage removal. The NFSC increased significantly in the endotracheal aspiration and line catheterization groups, whereas COMFORT and Ramsay scales showed significant changes in the catheter/drainage removal group (Table 5).
Table 4 Evolution of the hemodynamic, clinical scales, BIS, and NFSC values in cardiac and noncardiac patientsa
Cardiac patients HR (beats per minute) SBP (mm Hg) DBP (mm Hg) Ramsay COMFORT NRS (FNR, CNR) BIS NFSC Noncardiac patients HR (beats per minute) SBP (mm Hg) DBP (mm Hg) Ramsay COMFORT NRS (FNR, CNR) BIS NFSC
Table 5 Evolution of the hemodynamic, clinical scales, BIS, and NFSC values in the different techniques groups
Basal
Maneuver
Final
P, basal maneuver
Mean, SD
Mean, SD
Mean, SD
127.3 (29.2) 97.9 (17.3) 56.7 (14.9) 4.6 (2.7) 18.9 (6.4) 2.6 (2.3) 70.9 (23.7) 0.08 (0.17)
132.2 (18.9) 95.6 (20.6) 55.8 (20.6) 5.8 (2) 18.2 (4.9) 3.8 (2.8) 68.2 (23.2) 0.15 (0.2)
130 (19.8) 92.8 (19.3) 52.9 (12.7) 5.1 (2.3) 17.5 (4.7) 2.6 (2.2) 64.4 (24.6) 0.07 (0.14)
.02 .94 .206 .002 .217 .025 .604 .027
126.9 (30) 105.1 (16.7) 56.3 (16.2) 4.8 (3.1) 19.5 (8.3) 3.4 (3.1) 66.2 (27.3) 0.08 (0.16)
132.9 (26.7) 106.7 (17.7) 60.3 (17.1) 5.6 (2.6) 18.1 (7.9) 4.1 (3) 65.1(28.7) 0.1 (0.1)
133.6 (29.6) 108.5 (20.4) 57.2 (9.7) 5.7 (2.4) 18.1 (7.8) 3.2 (2.4) 64.4 (24.6) 0.01 (0.02)
.66 .14 .055 .516 .618 .635 .894 .309
SBP, systolic blood pressure; DBP, diastolic blood pressure; NRS, numeric rating scale, FNR, faces rating scale; CNR, color rating scale; BIS, biespectral index; NFCS, number of fluctuations of skin conductance. *Statistically significant p b 0.05. a Heart rate (beats per minute).
3.6. Correlation between NFSC, clinical scales, and BIS Positive moderate correlation between NFSC and BIS (r2 = 0.32; P = .03), COMFORT (r 2 = 0.45; P = .001), and SRPS scales (r 2 = 0.32; P = .016) existed. Negative correlation between NFSC and Ramsay scale (r 2 = − 0.41; P = .01) also occurred. There was no correlation with the dose of sedation received during the procedure. An increase in the NFSC concurred with a change in clinical scales in 15 patients and with BIS in 9 patients. However, the change in the NFSC only preceded changes in clinical scales in 2 patients, and it was not accompanied by changes in the BIS. No correlation was shown between these variables in patients treated with neuromuscular blockers. During the time of the study, some patients (nonregistered) showed artifacts related to movements. 4. Discussion Our study shows that, during invasive procedures in critically ill children HR, SRPS and Ramsay punctuation, and NFSC increased slightly but significantly in nonmuscle-relaxed patients but not in patients receiving muscular blockers. Although our study showed a statistically significant increase in NFSC during the procedure, very few children presented an increase in this parameter, and it never reached a level of 0.21 peaks per second, which is the level that correlates with pain according to the manufacturer's instructions. The slight increase in the NFSC could be related to an adequate level of sedation and analgesia of patients or because the algesimeter is not sensitive enough. A previous study by Gjerstad et al [5] in children with mechanical ventilation undergoing tracheal aspiration also revealed a significant
MJ. Solana et al. / Journal of Critical Care 30 (2015) 481–485
increase in the NFSC. However, as in our study, the increase in this parameter was very small (median, 0.045 peaks per second; range, 0.000-0.18), and it never reached the theoretical threshold of pain or anxiety. When comparing SC with clinical scales, we found a moderate correlation between the NFSC and COMFORT [5] and SRPS scales [24]. However, changes in NFSC only preceded clinical scales in 2 patients. We consider that the fact that NFSC does not precede clinical scales is very important to assess real usefulness of this device, although it has never been described. Movement artifacts due to the utilization of electrodes may occur [25], which are due to the alternancy of resistance or conductance in the electrode surface as a result of movement or changes in pressure [26]. A moderate number of artifacts caused by movement of the electrodes was registered in the nonmuscle-relaxed group. These measurements were excluded from the analysis. These artifacts have not been reported as a problem in previous studies [5]. Although hemodynamic variables are not consider as good indicators of pain in critical patients, as they can be artifacted by many other reasons, [2] we found slight but statistical significant changes in HR and SBP during painful procedures. Some pediatric critical patients need deep sedation or muscular blockers. Monitoring the level of sedation or pain in these patients is complex, as clinical scales are not very useful [6,9]. Bispectral index is a useful method for monitoring the level of sedation in children [27] including pediatric critical patients with deep sedation or muscular blockers [28-30] or postoperative cardiac patients [31]. Several studies have analyzed the correlation between BIS and clinical scales [30,3236]. The correlation between BIS and SC has been studied in adult patients during surgery, finding positive correlation between both techniques [37]. Our data show slight positive correlation between both methods in nonmuscle-relaxed patients but not in patients receiving muscular blockers. Our study has some limitations such as the small sample size, especially in the muscle-relaxed group, and the lack of a suitable tool to compare it, as clinical scales are not good indicators of the level of sedation.
[9]
[10] [11] [12]
[13]
[14] [15]
[16] [17]
[18]
[19] [20]
[21] [22]
[23] [24]
[25]
[26]
5. Conclusions [27]
The NFSC shows a slight but significant increase during invasive procedures in nonmuscle-relaxed pediatric critical patients but not in muscle-relaxed patients. Skin conductance has not proven to be more sensitive or faster than clinical scales, so it does not grant any advantages over hemodynamic parameters, clinical scales, or BIS in clinical practice. On the other hand, SC is not sensitive enough in patients with muscular blockers, although more studies are needed to confirm these results. References [1] Cidoncha E, Mencía S, Riaño B, Urbano J, López-Herce J, Carrillo A. The assessment of sedation in the critically ill child on mechanical ventilation during tracheal suction. An Pediatr (Barc) 2009;70:218–22. [2] Lamas A, López-Herce J. Monitoring sedation in the critically ill child. Anaesthesia 2010;65:516–24. [3] Carrasco G. Instruments for monitoring intensive care unit sedation. Crit Care 2000; 4:217–25. [4] Anand KJ, Sippell WG, Aynsley-Green A. Pain, anesthesia and babies. Lancet 1987;2: 1210–2. [5] Gjerstad AC, Wagner K, Henrichsen T, Storm H. Skin conductance versus the modified COMFORT sedation score as a measure of discomfort in artificially ventilated children. Pediatrics 2008;122:848–53. [6] De Jonghe B, Cook D, Appere-De-Vecchi C, Guyatt G, Meade M, Outin H. Using and understanding sedation scoring systems: a systematic review. Intensive Care Med 2000;26:275–85. [7] White PF, Boyle WA. Relationship between hemodynamic and electroencephalographic changes during general anesthesia. Anesth Analg 1989;68:177–81. [8] Schmidt NG, Bischoff P, Standln T, Jensen K, Voigt M, Schulte AM, et al. Narcotrend and bispectral index monitor are superior to classic electroencephalographic
[28]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
[36]
[37]
485
parameters for the assessment of anesthetic states during propofol-remifentanil anesthesia. Anesthesiology 2003;99:1072–7. Ista E, Van Dijk M, Tibboel D, de Hoog M. Assessment of sedation levels in pediatric intensive care patients can be improved by using the COMFORT behaviour scale. Pediatr Crit Care Med 2005;6:58–63. Dahaba AA. Different conditions that could result in the bispectral index indicating an incorrect hypnotic state. Anesth Analg 2005;101:765–73. Gallagher JD. Pacer-induced artifact in the bispectral index during cardiac surgery. Anesthesiology 1999;90:636. Hemmerling TM, Fortier JD. Falsely increased bispectral index values in a series of patients undergoing cardiac surgery using forced-air-warming therapy of the head. Anesth Analg 2002;95:322–3. Hemmerling TM, Migneault B. Falsely increased bispectral index during endoscopic shoulder surgery attributed to interferences with the endoscopic shaver device. Anesth Analg 2002;95:1678–9. Edelberg A. Electrical properties of the skin. In: Brown CC, editor. Methods in psychophysiology. Baltimore: Williams & Wilkins; 1967. p. 1–53. Ledowski T, Paech MJ, Storm H, Jones R, Schug SA. Skin conductance monitoring compared with biespectral index® monitoring to assess emergence from general anaesthesia using sevoflurane and remifentanil. BJA 2006;23:1–5. Hellerud BC, Storm H. Skin conductance and behaviour during sensory stimulation of preterm and term infants. Early Hum Dev 2002;70:35–46. Eriksson M, Storm H, Fremming A, Schollin J. Skin conductance compared to a combined behavioural and physiological pain measure in newborn infants. Acta Paediatr 2008;97:27–30. Ledowski T, Bromilow J, Wu J, Paech MJ, Storm H, Schug SA. The assessment of postoperative pain by monitoring skin conductance: results of a prospective study. Anaesthesia 2007;62:989–93. Strehle EM, Gray WK. Comparison of skin conductance measurements and subjective pain scores in children with minor injuries. Acta Paediatr 2013;102(11):502–6. Günther AC, Bottai M, Schandl AR, Storm H, Rossi P, Sackey PV. Palmar skin conductance variability and the relation to stimulation, pain and the motor activity assessment scale in intensive care unit patients. Crit Care 2013;17:R51. Storm H. Changes in skin conductance as a tool to monitor nociceptive stimulation and pain. Curr Opin Anaesthesiol 2008;21:796–804. Agrawal D, Feldman HA, Krauss B, Waltzman ML. Bispectral index monitoring quantifies depth of sedation during emergency department procedural sedation and analgesia in children. Ann Emerg Med 2004;43:247–55. Ambuel B, Hamlett KW, Marx CM, Blumer JL. Assessing distress in pediatric intensive care environments: the COMFORT scale. J Pediatr Psychol 1992;17:95–109. Choo EK, Magruder WMA, Montgomery CJ, Lim J, Brant R, Ansermino JM. Skin conductance fluctuations correlate poorly with postoperative self-report pain measures in school-aged children. Anesthesiology 2010;113:175–82. Røeggen I, Harrison D, Loughnan P, Storm H, Smith Katherine, Johnston L. Skin conductance variability between and within hospitalised infants at rest. Early Hum Dev 2011;87:37–42. Hagbarth KE, Hallin RG, Hongell A, Torebjörk HE, Wallin BG. General characteristics of sympathetic activity in human skin nerves. Acta Physiol Scand 1972; 84:164–76. Lamas A, López-Herce J, Sancho L, Mencía S, Carrillo A, Santiago MJ, et al. Bispectral index and middle latency auditory evoked potentials in children younger than twoyears-old. Anesth Analg 2008;106:426–32. Lamas A, López-Herce J, Sancho L, Mencía S, Carrillo A, Santiago MJ, et al. Analysis of bispectral index and middle latency auditory-evoked potentials parameters in critically ill children. J Clin Neurophysiol 2009;26:150–4. Lamas A, López-Herce J, Sancho L, Mencía S, Carrillo A, José Santiago M, et al. Responsiveness to stimuli of bispectral index, middle latency auditory evoked potentials and clinical scales in critically ill children. Anaesthesia 2008;63:1296–301. Lamas A, López-Herce J, Sancho L, Mencía S, Carrillo A, Santiago MJ, et al. Assessing sedation in critically ill children by bispectral index, auditory-evoked potentials and clinical scales. Intensive Care Med 2008;34:2092–9. Lamas A, López-Herce J, Sancho L, Mencía S, Carrillo A, Santiago MJ, et al. Assessment of the level of sedation in children after cardiac surgery. Ann Thorac Surg 2009; 88(1):44–50. Aneja R, Heard AM, Fletcher JE, Heard CM. Sedation monitoring of children by the bispectral index in the pediatric intensive care unit. Pediatr Crit Care Med 2003;4: 60–4. Tonner PH, Wei C, Bein B, Weiler N, Paris A, Scholz J. Comparison of two bispectral index algorithms in monitoring sedation in postoperative intensive care patients. Crit Care Med 2005;33:580–4. Courtman SP, Wardurgh A, Petros AJ. Comparison of the bispectral index monitor with the COMFORT score in assessing level of sedation of critically ill children. Intensive Care Med 2003;29:2239–46. Triltsch AE, Nestmann G, Orawa H, Moshirzadeh M, Sander M, Grosse J, et al. Bispectral index versus COMFORT score to determine the level of sedation in paediatric intensive care unit patients: a prospective study. Crit Care 2005;9:9–17. Trope RM, Silver PC, Sagy M. Concomitant assessment of depth of sedation by changes in bispectral index and changes in autonomic variables (heart rate and/or BP) in pediatric critically ill patients receiving neuromuscular blockade. Chest 2005;128: 303–7. Storm H, Myre K, Rostrup M, Stokland O, Lien MD, Raeder JC. Skin conductance correlates with perioperative stress. Acta Anaesthesiol Scand 2002;46:887–95.
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Assessment of pain in critically ill children. Is cutaneous conductance a reliable tool?☆ M.J. Solana, MD, PhD a,b,⁎, J. Lopez-Herce, MD, PhD a,b, S. Fernandez, MD a,b, R. Gonzalez, MD a,b, J. Urbano, MD, PhD a,b, J. Lopez, MD a,b, J.M. Bellon, PhD b a b
Pediatric Intensive Care Service, Hospital General Universitario Gregorio Marañón, Dr Castelo 47, 28009 Madrid, Spain Instituto de Investigación del Hospital Gregorio Marañón, Doctor Esquerdo 46, 28009 Madrid, Spain
a r t i c l e
i n f o
Keywords: Pain Children Skin conductance Sedation Monitoring Critical care
a b s t r a c t Purpose: The purpose of this study is to assess the usefulness and accuracy of skin conductance (SC) as a tool to evaluate the level of sedation and pain in pediatric critical patients during painful procedures and to compare it with hemodynamic variables, clinical scales, and bispectral index (BIS). Materials and methods: This is a prospective observational study in 61 critical children undergoing invasive procedures. Hemodynamic data (heart rate and arterial blood pressure), clinical scales punctuation (Ramsay, COMFORT, and numeric rating pain scales), BIS, and the number of fluctuations of SC per second were collected before, during, and at the end of the procedure. Results: The mean age of the patients was 42.9 (range, 1 month to 16 years). Seventy-two point six percent were postcardiac surgery patients. Nonmuscle-relaxed patients showed a moderate increase in heart rate (P = .02), numeric rating pain scales (P = .03), and Ramsay scale (P = .002). The number of fluctuations of SC per second increased significantly during the procedure (basal, 0.1; maneuver, 0.2; P = .015), but it never reached the level considered as pain or stress nor did it precede clinical scales or BIS. None of the variables studied showed a significant change during the procedure in muscle-relaxed patients. Conclusions: Skin conductance was not found to be more sensitive or faster than clinical scales for the assessment of pain or stress in critical children undergoing painful procedures. Skin conductance was not useful in musclerelaxed children. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Children admitted to a pediatric intensive care unit are commonly subjected to painful procedures and stressful situations that require the administration of sedative and/or analgesic drugs [1]. The management of sedation in these patients is difficult because sedative drugs have a narrow therapeutic window, and patients frequently have altered mechanisms of hepatic and renal clearance and because critically ill children cannot adequately verbalize the intensity and site of pain and have more tolerance and physical dependence than adults [2]. Anatomic and neurochemic pathways for the transmission of pain are developed at birth, and children can respond to it with physiologic, metabolic, hormonal, and behavioral changes. Pain causes hemodynamic instability, hypoxemia, and it increases intracranial ☆ This study was funded by a scholarship of the Madrid and Castilla La Mancha Pediatric Society, Madrid, Spain. ⁎ Corresponding author. Servicio de Cuidados Intensivos Pediátricos Hospital General Universitario Gregorio Marañón Dr Castelo 47 28009 Madrid, Spain. Tel.: + 34 915290327; fax: +34 915868018. E-mail addresses: [email protected] (M.J. Solana), [email protected] (J. Lopez-Herce), [email protected] (S. Fernandez), [email protected] (R. Gonzalez), pazienziainfi[email protected] (J. Urbano), [email protected] (J. Lopez), [email protected] (J.M. Bellon). http://dx.doi.org/10.1016/j.jcrc.2015.01.008 0883-9441/© 2015 Elsevier Inc. All rights reserved.
pressure. On the other hand, excessive sedation can cause cardiac and respiratory depression, an increase in the duration of mechanical ventilation and abstinence syndrome [3,4]. Continuous monitoring of the level of sedation or pain in critically ill children is imperative during painful procedures, to find the right balance between being without discomfort and not being oversedated [5]. Several methods have been used for the evaluation of the level of sedation in critical patients, although no criterion standard exists [3,6]. Hemodynamic variables, clinical scales, and analysis of the electroencephalogram 1(EEG) are the most widely used methods [2]. However, these methods have some limitations. Hemodynamic parameters are influenced by the volemic status of the patient, drugs, and the autonomous nervous system [7,8]. Sedation scales are subjective methods and cannot be applied in profoundly sedated or musclerelaxed patients [6,9] In the last years, new methods based on the analysis of the EEG have been developed. Bispectral index (BIS) is a noninvasive method that assesses the level of consciousness of the patient by analyzing the frequencies of the EEG waves. Although it has been proven to be a useful 1 EEG: electroencephalogram; 2 BIS: biespectral index;3 NFSC: number of fluctuations of skin conductance per second; 4 SRPS: Faces Pain Scale-revised; 5HR: heart rate; 6SBP: systolic blood pressure; 7DBP: diastolic blood pressure; 8RR: respiratory rate.
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method in critical patients, it also has some limitations: several clinical conditions and electronic devices like pacemakers could induce artifact signal pollution [2,10-13]. Skin conductance (SC) is a noninvasive method for the evaluation of pain or stress [5,14,15]. Pain or stress produces an increase in subcortical and cortical activity, which generates a sympathetic download that releases acetylcholine that acts on the muscharinic receptors, which stimulate sweat gland secretion, resulting in changes in SC [14]. The peak of the SC appears 1 to 2 seconds after a stimulus and is, in theory, independent of temperature, muscle relaxation, sympathomimetic drugs, or changes in the volume status of the patient. Skin conductance seems to be useful for monitoring the level of sedation or pain in preterms and infants [16,17], postsurgical patients [18], children with minor injuries [19], with mechanical ventilation [5], and critically ill adult patients [20]. However, there are few data related to the usefulness of this device in critically ill children [5], and there is not much experience in muscle-relaxed patients. The purposes of this study were to evaluate the usefulness and accuracy of this device for the assessment of the level of sedation and analgesia during painful procedures in a pediatric critical care unit; to compare this method with hemodynamic variables, clinical scales, and BIS during painful procedures; and, finally, to determine the usefulness of SC in pediatric muscle-relaxed patients. 2. Material and methods 2.1. Participants We conducted a prospective, observational study, which included critically ill children aged from 1 month to 16 years undergoing a painful technique. Painful procedures included arterial or central venous line catheter insertion, urinary tract catheterization, insertion of a nasogastric tube, tracheal aspiration, pleural catheter removal, left atrial pressure catheter removal, lumbar puncture, or sternal closure. Approval was obtained from the institutional review boards of the hospital, and informed consent was obtained from the parent or legal guardian of each child enrolled. Patients were excluded if they were being treated with anticholinergic drugs (high-dose atropine or neostigmine) or sympathetic central nervous system inhibitors (ie, clonidine), if they had a peacemaker or defibrillator, or if they rejected to participate in the study. 2.2. Test methods After being included in the study, a BIS XP 3.4 monitor (Aspect Medical Systems, Newton, MA) was settled. Frontal sensors with 3 ZIP Prep pediatric electrodes in children younger than 1 year and Quatro ZIP Prep electrodes in children older than 1 year were used. The BIS monitor was connected to a Philips Intellivue MP70 monitor. Skin conductance was analyzed by a Med-Storm monitor (MedStorm Innovation AS, Oslo, Norway). This device measure real-time changes in SC due to pain or stress by analyzing the peaks or number of fluctuations of SC per second (NFSC) and the relative area under the curve [21]. An NFSC peak is defined as minimum followed by a maximum in conductance values Micro Siemens (μS) [5,21]. The system can measure conductance values in the range of 1 to 200 μS, with a noise level below 0.002 μS and has error detection that provides a warning about electrode looses or external interferences [21]. An applied voltage of 50 mV and a 3-electrode system (Sensormedics, CA, Oslo, Norway) were used. The 3-electrode system comprised a measuring electrode (M), a countercurrent electrode (C), and a reference voltage electrode (R), which ensured a constant applied voltage across the stratum corneum. The electrodes were settled on the soles in children younger than 1 year and on the palms in older children to improve the quality of the signal, as older children have a thicker sole corneal stratum than infants.
The electrodes were placed according to the Edelberg guidelines for the placement of electrodes to obtain the most sensitive measurement [14]. According to the specifications of the manufacturer, a value greater than 0.21 peaks per second was considered to be as pain or discomfort. 2.2.1. Clinical scales Anxiety and pain were measured by the Modified Ramsay scale, COMFORT scale, and self-report pain scale (SRPS) (Faces Pain ScaleRevised in infants and children after receiving sedatives and color rating scale for conscious children). Modified Ramsay scale is an 8-point scoring system, which quantifies the level of sedation [22] and has been used to evaluate the level of sedation during the performance of procedures in critically ill adults and children [2,3,6,22]. This scale is scored from 1 (patient anxious and agitated or restless or both) to 8 (no response to any stimulus including pain). The COMFORT scale is a useful score to measure the levels of stress in critically ill children requiring mechanical ventilation [23]. It evaluates 8 parameters, scoring between 1 and 5 points each. 2.3. Protocol Previous to the procedure, heart rate (HR [beats per minute]), systolic (SBP [millimeter of mercury]) and diastolic arterial blood pressure (DBP [millimeter of mercury]), and respiratory rate (breaths per minute) were recorded as well as the punctuation in clinical scales, BIS, and NFSC. All these measures were repeated during the procedure and 5 minutes after the procedure. Maximum registered values of the procedure were recorded and considered for analysis. The basal pharmacologic sedation-analgesia treatment (type and dosage) of the patient as well as the additional doses needed to achieve a good level of analgesia was also recorded. The administration of additional doses was at the discretion of the attending physician based on the clinical status of the patient. 2.4. Statistical methods Data were analyzed with SPSS software version 18.0. The evolution of hemodynamic parameters, clinical scales, BIS, and NFSC were analyzed using the Wilcoxon test. Correlation between variables was estimated using the Spearman rank correlation coefficient (ρ). 3. Results Sixty-one patients were included in the study. The mean age was 42.9 ± 56.5 months. Children were diagnosed as postcardiac surgery in 72.6%, respiratory failure in 9.7%, neurologic disease in 6.5%, oncology patients in 6.5%, sepsis in 3.2%, and others in 1.6%. The most common procedure was pleural or atrial left pressure catheter removal (37.7%), followed by arterial or venous canalization (27.8%), tracheal tube aspiration (18%), nasogastric or urinary tract tube insertion (9.8%), lumbar puncture (4.9%), and chest closure in a cardiac patient (1.6%). Continuous midazolam infusion was used in 42% of patients (mean dose, 1.5 ± 2.4 μg/kg per minute), fentanyl infusion in 61% (mean dose, 1.0 ± 1.2 μg/kg per hour), remifentanil infusion in 6% (mean dose, 0.05 ± 0.2 μg/kg per minute), and propofol infusion in 22% of patients (mean dose, 0.6 ± 1.3 mg/kg per hour). Fifteen patients received continuous muscle relaxation with vecuronium (mean dose, 0.13 ± 0.1 mg/kg per hour). 3.1. Evolution of hemodynamic parameters, clinical scales, BIS, and NFSC variables The evolution of hemodynamics, clinical scales, BIS, and NFSC in basal situation, during the procedure and at the end of the procedure is registered in Table 1. The NFSC evolution is represented in Figure 1.
MJ. Solana et al. / Journal of Critical Care 30 (2015) 481–485 Table 1 Evolution of the hemodynamic, clinical scales, BIS, and NFSC values
HR (beats per minute)a SBP (mm Hg) DBP (mm Hg) Ramsay COMFORT NRS (FNR, CNR) BIS NFSC
Basal
Maneuver
Final
Mean, SD
Mean, SD
Mean, SD
127.6 (29.05) 99.7 (17.2) 56.4 (15) 4.6 (2.8) 19 (6.9) 2.9 (2.7) 69.7 (24.4) 0.09 (0.17)
132.8 (21) 98.4 (20.2) 56.7 (14.9) 5.7 (2.2) 18.2 (5.8) 3.9 (2.8) 67.4 (24.4) 0.14 (0.18)
131.2 (22.3) 96.4 (20.3) 53.7 (12.2) 5.2 (2.4) 17.7 (5.7) 2.6 (2.3) 68.1 (24.4) 0.6 (0.1)
P, basal maneuver .019 .425 .763 .020 .252 .039 .504 .017
NRS indicates numeric rating scale; FNR, faces rating scale; CNR, color rating scale; HR(bpm), heart rate (beats per minute); SBP, systolic blood pressure; DBP, diastolic blood pressure; NRS, numeric rating scale, FNR, faces rating scale; CNR, color rating scale; BIS, biespectral index; NFCS, number of fluctuations of skin conductance. a Heart rate (beats per minute).
During the procedure, the NFSC and the SRPS scale increased in 25 patients (41%), the COMFORT scale increased in 10 (18%), BIS increased in 19 children (40%), and the Ramsay scale decreased in 8 patients (13%). A statistically significant increase in HR, Ramsay, and SRPS scales and the NFSC between the baseline situation and the procedure were observed. No significant changes were observed in the remaining analyzed parameters (Table 1).
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Table 2 Evolution of the hemodynamic, clinical scales, BIS, and conductance values in nonmusclerelaxed and muscle-relaxed patientsa Basal
Maneuver
Final
P⁎
Mean, SD
Mean, SD
Mean, SD
Basal maneuver
132.4 (18.6) 100 (2.1) 59.4 (14.4) 5.1 (2.1) 20.3 (5.2) 4.8 (2.6) 78.8 (18.2) 0.2 (1.6)
130.4 (20.7) 97.8 (19.6) 55.5 (11.9) 4.5 (2.2) 19.5 (5.1) 3.2 (2.3) 79.5 (19.5) 0.1 (0.8)
.026 .191 .846 .002 .514 .037 .28 .015
136.1 (22.1) 95.3 (18.7) 49.6 (12.9) 7.7 (1) 12.4 (3) 1.2 (1.4) 40.8 (15.1) 0.02 (0.05)
133.5 (27.7) 92 (22.3) 48.1 (11.9) 7.2 (1.5) 12.2 (2.8) 1.3 (1.5) 44.5 (10.5) 0 (0)
.64 .227 .385 1 .514 .655 .271 .785
Nonmuscle-relaxed patients HR (beats per minute) 127.5 (29.4) SBP (mm Hg) 100.2 (17.2) DBP (mm Hg) 58.6 (15) Ramsay 3.6 (2.4) COMFORT 21.5 (6.5) NRS (FNR, CNR) 3.5 (2.8) BIS 78.8 (21.6) NFSC 0.1 (1.5) Muscle-relaxed patients HR (beats per minute) 128.7 (26.9) SBP (mm Hg) 99.2 (18.4) DBP (mm Hg) 50.9 (12.1) Ramsay 7.7 (1) COMFORT 12.4 (3) NRS (FNR, CNR) 1.3 (1.6) BIS 47.2 (12.3) NFSC 0.02 (0.04)
SBP, systolic blood pressure; DBP, diastolic blood pressure; NRS, numeric rating scale, FNR, faces rating scale; CNR, color rating scale; BIS, biespectral index; NFCS, number of fluctuations of skin conductance. ⁎ Statistically significant p b 0.05. a Heart rate (beats per minute).
3.2. Comparison between muscle-relaxed and nonmuscle-relaxed patients The evolution of hemodynamic parameters, clinical scales, BIS, and NFSC in basal situation and during the procedure in muscle-relaxed and nonmuscle-relaxed patients is registered in Table 2. The NFSC, Ramsay, and SRPS scales increased significantly during the procedure in the nonmuscle-relaxed group. None of the parameters presented significant changes in the muscle-relaxed group during the procedure. Only 3 of the muscle-relaxed patients showed changes in the NFSC, but they were not significant. Two of these patients had a slight increase in the NFSC, and the third one presented a decrease in the NFSC that coincided with a drop in BIS punctuation.
vs 1 ± 1.3 μg/kg per hour; remifentanil, 0.1 ± 0.3 vs 0 μg/kg per minute; propofol, 0.6 ± 1.4 vs 0.6 ± 1.3 mg/kg per hour). The evolution of hemodynamic parameters, BIS, clinical scales, and NFSC between both groups of age is reflected in Table 3. Children younger than 12 months showed significant changes in the HR and Ramsay score during the procedure, whereas children older than 12 months presented significant changes in the systolic and diastolic blood pressure, the clinical scales, and the NFSC. None of the groups of age showed significant differences in the BIS value during the procedure.
3.3. Evolution of the variables according to age
3.4. Evolution of variables according to diagnosis
Twenty-seven patients were younger than 12 months. Forty point seven percent of the children younger than 12 months and 12% of the children 12 months or older were muscle-relaxed, although no significant differences in the dosage of sedation existed between both groups (midazolam, 1.8 ± 2.3 vs 1.3 ± 2.5 μg/kg per minute; fentanyl, 1.1 ± 1.3
Patients were divided into 2 groups regarding diagnosis: postoperatory cardiac patients and other diagnosis (Table 4). Cardiac patients showed significant changes in HR, Ramsay and SRPS scales, and NFSC during the procedure, whereas noncardiac patients showed significant changes only in diastolic pressure during the maneuver.
Figure 1. Evolution of the NFSC in total population and in muscle and nonmuscle-relaxed patients.
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Table 3 Evolution of the hemodynamic, clinical scales, BIS and NPPS values in children younger than 12 months and children 12 months or oldera
Children b12 mo HR (beats per minute) SBP (mm Hg) DBP (mm Hg) Ramsay COMFORT NRS (FNR, CNR) BIS NFSC Children ≥12 mo HR (beats per minute) SBP (mm Hg) DBP (mm Hg) Ramsay COMFORT NRS (FNR, CNR) BIS NFSC
Basal
Maneuver
Final
P⁎
Basal
Maneuver
Final
P⁎
Mean, SD
Mean, SD
Mean, SD
Basal maneuver
Mean, SD
Mean, SD
Mean, SD
Basal maneuver
136.3 (20.9) 95.4 (16.9) 54.4 (11.6) 4.7 (2.9) 19.2 (7.8) 3.2 (3.1) 68.2 (24.8) 0.12 (1.1)
139.2 (16) 90.2 (15.7) 52.4 (11.4) 5.8 (2.1) 16.7 (4.7) 3.03 (2.4) 61.9 (25.4) 0.17 (1.3)
136.8 (18.1) 88.6 (19.3) 50.3 (10.6) 2.4 (2.7) 16.4 (4.7) 2.7 (2.2) 63.5 (20.3) 0.09 (0.6)
.027 .327 .871 .012 .161 .682 .413 .529
125.7 (16.8) 98.3 (15.3) 57.5 (18.9) 6.1 (3.3) 17.6 (10.4) 2.7 (3.6) 53.9 (26.7) 0.2 (0.3)
120.8 (22.2) 88.8 (10.8) 49.3 (9.9) 2.1 (2.9) 16.8 (9.6) 2.1 (2.9) 54.6 (22.4) 0.1 (0.2)
.122 .003 .011 1 .443 .18 .544 .042
120.2 (32.7) 103.7 (17.2) 58.9 (16.8) 4.4 (2.7) 19.3 (6.5) 2.7 (2.4) 71.3 (23.8) 0.06 (0.6)
127.8 (20.7) 106.3 (21.6) 61.3 (16) 5.6 (2.3) 19.6 (6.4) 4.7 (3) 73.4 (22.7) 0.1 (0.6)
126.3 (25) 103 (19.4) 56.9 (12.9) 5.2 (2.2) 18.6 (6.3) 2.8 (2.4) 74.8 (23.2) 0.04 (0.3)
.306 .004 .05 .047 .066 .02 .109 .003
135 (16.2) 98.1 (22.4) 55.9 (14.8) 5.9 (1.1) 17.4 (3.3) 4.1 (2.8) 66.3 (23.3) 0.1 (0.1)
134.3 (20.3) 103.3 (24.5) 56.1 (12.5) 5.8 (2.2) 16.8 (4) 2.8 (2.3) 67.1 (18.8) 0 (0.1)
.699 .123 .935 .495 .439 .091 .98 .039
133.7 (20.2) 97.7 (22.4) 54.7 (11.7) 5.3 (2) 19.2 (4.4) 4.3 (2.5) 79.9 (17.4) 0.1 (0.2)
132.2 (20.3) 93.9 (20.4) 52.5 (12.4) 4.1 (1.9) 19.1 (4.1) 3 (1.9) 80.7 (15.9) 0.1 (0.2)
.502 .161 .565 .001 .013 .476 .949 .465
SBP, systolic blood pressure; DBP, diastolic blood pressure; NRS, numeric rating scale, FNR, faces rating scale; CNR, color rating scale; BIS, biespectral index; NFCS, number of fluctuations of skin conductance. ⁎ Statistically significant p b 0.05. a Heart rate (beats per minute).
None of the 2 groups presented significant changes in the BIS or in the COMFORT punctuation.
Traqueal aspiration HR (beats per minute) 119.2 (21.5) SBP (mm Hg) 101.3 (13.3) DBP (mm Hg) 59.3 (20.6) Ramsay 6.1 (3.3) COMFORT 16 (8.6) NRS (FNR, CNR) 1.7 (2.5) BIS 59.3 (22.1) NFSC 0.1 (0.1) Catheter insertion HR (beats per minute) 131.3 (21.5) SBP (mm Hg) 97.9 (21.1) DBP (mm Hg) 56.6 (14.9) Ramsay 5.4 (2.7) COMFORT 18.4 (5.4) NRS (FNR, CNR) 2.5 (2) BIS 66.9 (23.4) NFSC 0 (0) Pleural catheter insertion/removal HR (beats per minute) 130.1 (35.4) SBP (mm Hg) 98.5 (16.1) DBP (mm Hg) 54.1 (11.6) Ramsay 3 (2) COMFORT 22.5 (6.7) NRS (FNR, CNR) 3.7 (3) BIS 81.2 (20.8) NFSC 0.1 (0.2)
HR(bpm), heart rate (beats per minute); SBP, systolic blood pressure; DBP, diastolic blood pressure; NRS, numeric rating scale, FNR, faces rating scale; CNR, color rating scale; BIS, biespectral index; NFCS, number of fluctuations of skin conductance. ⁎ Statistically significant p b 0.05.
3.5. Evolution of variables according to the technique Patients were divided into 3 groups according to the technique: endotracheal aspiration, central and peripheral line insertion, and catheter/drainage removal. The NFSC increased significantly in the endotracheal aspiration and line catheterization groups, whereas COMFORT and Ramsay scales showed significant changes in the catheter/drainage removal group (Table 5).
Table 4 Evolution of the hemodynamic, clinical scales, BIS, and NFSC values in cardiac and noncardiac patientsa
Cardiac patients HR (beats per minute) SBP (mm Hg) DBP (mm Hg) Ramsay COMFORT NRS (FNR, CNR) BIS NFSC Noncardiac patients HR (beats per minute) SBP (mm Hg) DBP (mm Hg) Ramsay COMFORT NRS (FNR, CNR) BIS NFSC
Table 5 Evolution of the hemodynamic, clinical scales, BIS, and NFSC values in the different techniques groups
Basal
Maneuver
Final
P, basal maneuver
Mean, SD
Mean, SD
Mean, SD
127.3 (29.2) 97.9 (17.3) 56.7 (14.9) 4.6 (2.7) 18.9 (6.4) 2.6 (2.3) 70.9 (23.7) 0.08 (0.17)
132.2 (18.9) 95.6 (20.6) 55.8 (20.6) 5.8 (2) 18.2 (4.9) 3.8 (2.8) 68.2 (23.2) 0.15 (0.2)
130 (19.8) 92.8 (19.3) 52.9 (12.7) 5.1 (2.3) 17.5 (4.7) 2.6 (2.2) 64.4 (24.6) 0.07 (0.14)
.02 .94 .206 .002 .217 .025 .604 .027
126.9 (30) 105.1 (16.7) 56.3 (16.2) 4.8 (3.1) 19.5 (8.3) 3.4 (3.1) 66.2 (27.3) 0.08 (0.16)
132.9 (26.7) 106.7 (17.7) 60.3 (17.1) 5.6 (2.6) 18.1 (7.9) 4.1 (3) 65.1(28.7) 0.1 (0.1)
133.6 (29.6) 108.5 (20.4) 57.2 (9.7) 5.7 (2.4) 18.1 (7.8) 3.2 (2.4) 64.4 (24.6) 0.01 (0.02)
.66 .14 .055 .516 .618 .635 .894 .309
SBP, systolic blood pressure; DBP, diastolic blood pressure; NRS, numeric rating scale, FNR, faces rating scale; CNR, color rating scale; BIS, biespectral index; NFCS, number of fluctuations of skin conductance. *Statistically significant p b 0.05. a Heart rate (beats per minute).
3.6. Correlation between NFSC, clinical scales, and BIS Positive moderate correlation between NFSC and BIS (r2 = 0.32; P = .03), COMFORT (r 2 = 0.45; P = .001), and SRPS scales (r 2 = 0.32; P = .016) existed. Negative correlation between NFSC and Ramsay scale (r 2 = − 0.41; P = .01) also occurred. There was no correlation with the dose of sedation received during the procedure. An increase in the NFSC concurred with a change in clinical scales in 15 patients and with BIS in 9 patients. However, the change in the NFSC only preceded changes in clinical scales in 2 patients, and it was not accompanied by changes in the BIS. No correlation was shown between these variables in patients treated with neuromuscular blockers. During the time of the study, some patients (nonregistered) showed artifacts related to movements. 4. Discussion Our study shows that, during invasive procedures in critically ill children HR, SRPS and Ramsay punctuation, and NFSC increased slightly but significantly in nonmuscle-relaxed patients but not in patients receiving muscular blockers. Although our study showed a statistically significant increase in NFSC during the procedure, very few children presented an increase in this parameter, and it never reached a level of 0.21 peaks per second, which is the level that correlates with pain according to the manufacturer's instructions. The slight increase in the NFSC could be related to an adequate level of sedation and analgesia of patients or because the algesimeter is not sensitive enough. A previous study by Gjerstad et al [5] in children with mechanical ventilation undergoing tracheal aspiration also revealed a significant
MJ. Solana et al. / Journal of Critical Care 30 (2015) 481–485
increase in the NFSC. However, as in our study, the increase in this parameter was very small (median, 0.045 peaks per second; range, 0.000-0.18), and it never reached the theoretical threshold of pain or anxiety. When comparing SC with clinical scales, we found a moderate correlation between the NFSC and COMFORT [5] and SRPS scales [24]. However, changes in NFSC only preceded clinical scales in 2 patients. We consider that the fact that NFSC does not precede clinical scales is very important to assess real usefulness of this device, although it has never been described. Movement artifacts due to the utilization of electrodes may occur [25], which are due to the alternancy of resistance or conductance in the electrode surface as a result of movement or changes in pressure [26]. A moderate number of artifacts caused by movement of the electrodes was registered in the nonmuscle-relaxed group. These measurements were excluded from the analysis. These artifacts have not been reported as a problem in previous studies [5]. Although hemodynamic variables are not consider as good indicators of pain in critical patients, as they can be artifacted by many other reasons, [2] we found slight but statistical significant changes in HR and SBP during painful procedures. Some pediatric critical patients need deep sedation or muscular blockers. Monitoring the level of sedation or pain in these patients is complex, as clinical scales are not very useful [6,9]. Bispectral index is a useful method for monitoring the level of sedation in children [27] including pediatric critical patients with deep sedation or muscular blockers [28-30] or postoperative cardiac patients [31]. Several studies have analyzed the correlation between BIS and clinical scales [30,3236]. The correlation between BIS and SC has been studied in adult patients during surgery, finding positive correlation between both techniques [37]. Our data show slight positive correlation between both methods in nonmuscle-relaxed patients but not in patients receiving muscular blockers. Our study has some limitations such as the small sample size, especially in the muscle-relaxed group, and the lack of a suitable tool to compare it, as clinical scales are not good indicators of the level of sedation.
[9]
[10] [11] [12]
[13]
[14] [15]
[16] [17]
[18]
[19] [20]
[21] [22]
[23] [24]
[25]
[26]
5. Conclusions [27]
The NFSC shows a slight but significant increase during invasive procedures in nonmuscle-relaxed pediatric critical patients but not in muscle-relaxed patients. Skin conductance has not proven to be more sensitive or faster than clinical scales, so it does not grant any advantages over hemodynamic parameters, clinical scales, or BIS in clinical practice. On the other hand, SC is not sensitive enough in patients with muscular blockers, although more studies are needed to confirm these results. References [1] Cidoncha E, Mencía S, Riaño B, Urbano J, López-Herce J, Carrillo A. The assessment of sedation in the critically ill child on mechanical ventilation during tracheal suction. An Pediatr (Barc) 2009;70:218–22. [2] Lamas A, López-Herce J. Monitoring sedation in the critically ill child. Anaesthesia 2010;65:516–24. [3] Carrasco G. Instruments for monitoring intensive care unit sedation. Crit Care 2000; 4:217–25. [4] Anand KJ, Sippell WG, Aynsley-Green A. Pain, anesthesia and babies. Lancet 1987;2: 1210–2. [5] Gjerstad AC, Wagner K, Henrichsen T, Storm H. Skin conductance versus the modified COMFORT sedation score as a measure of discomfort in artificially ventilated children. Pediatrics 2008;122:848–53. [6] De Jonghe B, Cook D, Appere-De-Vecchi C, Guyatt G, Meade M, Outin H. Using and understanding sedation scoring systems: a systematic review. Intensive Care Med 2000;26:275–85. [7] White PF, Boyle WA. Relationship between hemodynamic and electroencephalographic changes during general anesthesia. Anesth Analg 1989;68:177–81. [8] Schmidt NG, Bischoff P, Standln T, Jensen K, Voigt M, Schulte AM, et al. Narcotrend and bispectral index monitor are superior to classic electroencephalographic
[28]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
[36]
[37]
485
parameters for the assessment of anesthetic states during propofol-remifentanil anesthesia. Anesthesiology 2003;99:1072–7. Ista E, Van Dijk M, Tibboel D, de Hoog M. Assessment of sedation levels in pediatric intensive care patients can be improved by using the COMFORT behaviour scale. Pediatr Crit Care Med 2005;6:58–63. Dahaba AA. Different conditions that could result in the bispectral index indicating an incorrect hypnotic state. Anesth Analg 2005;101:765–73. Gallagher JD. Pacer-induced artifact in the bispectral index during cardiac surgery. Anesthesiology 1999;90:636. Hemmerling TM, Fortier JD. Falsely increased bispectral index values in a series of patients undergoing cardiac surgery using forced-air-warming therapy of the head. Anesth Analg 2002;95:322–3. Hemmerling TM, Migneault B. Falsely increased bispectral index during endoscopic shoulder surgery attributed to interferences with the endoscopic shaver device. Anesth Analg 2002;95:1678–9. Edelberg A. Electrical properties of the skin. In: Brown CC, editor. Methods in psychophysiology. Baltimore: Williams & Wilkins; 1967. p. 1–53. Ledowski T, Paech MJ, Storm H, Jones R, Schug SA. Skin conductance monitoring compared with biespectral index® monitoring to assess emergence from general anaesthesia using sevoflurane and remifentanil. BJA 2006;23:1–5. Hellerud BC, Storm H. Skin conductance and behaviour during sensory stimulation of preterm and term infants. Early Hum Dev 2002;70:35–46. Eriksson M, Storm H, Fremming A, Schollin J. Skin conductance compared to a combined behavioural and physiological pain measure in newborn infants. Acta Paediatr 2008;97:27–30. Ledowski T, Bromilow J, Wu J, Paech MJ, Storm H, Schug SA. The assessment of postoperative pain by monitoring skin conductance: results of a prospective study. Anaesthesia 2007;62:989–93. Strehle EM, Gray WK. Comparison of skin conductance measurements and subjective pain scores in children with minor injuries. Acta Paediatr 2013;102(11):502–6. Günther AC, Bottai M, Schandl AR, Storm H, Rossi P, Sackey PV. Palmar skin conductance variability and the relation to stimulation, pain and the motor activity assessment scale in intensive care unit patients. Crit Care 2013;17:R51. Storm H. Changes in skin conductance as a tool to monitor nociceptive stimulation and pain. Curr Opin Anaesthesiol 2008;21:796–804. Agrawal D, Feldman HA, Krauss B, Waltzman ML. Bispectral index monitoring quantifies depth of sedation during emergency department procedural sedation and analgesia in children. Ann Emerg Med 2004;43:247–55. Ambuel B, Hamlett KW, Marx CM, Blumer JL. Assessing distress in pediatric intensive care environments: the COMFORT scale. J Pediatr Psychol 1992;17:95–109. Choo EK, Magruder WMA, Montgomery CJ, Lim J, Brant R, Ansermino JM. Skin conductance fluctuations correlate poorly with postoperative self-report pain measures in school-aged children. Anesthesiology 2010;113:175–82. Røeggen I, Harrison D, Loughnan P, Storm H, Smith Katherine, Johnston L. Skin conductance variability between and within hospitalised infants at rest. Early Hum Dev 2011;87:37–42. Hagbarth KE, Hallin RG, Hongell A, Torebjörk HE, Wallin BG. General characteristics of sympathetic activity in human skin nerves. Acta Physiol Scand 1972; 84:164–76. Lamas A, López-Herce J, Sancho L, Mencía S, Carrillo A, Santiago MJ, et al. Bispectral index and middle latency auditory evoked potentials in children younger than twoyears-old. Anesth Analg 2008;106:426–32. Lamas A, López-Herce J, Sancho L, Mencía S, Carrillo A, Santiago MJ, et al. Analysis of bispectral index and middle latency auditory-evoked potentials parameters in critically ill children. J Clin Neurophysiol 2009;26:150–4. Lamas A, López-Herce J, Sancho L, Mencía S, Carrillo A, José Santiago M, et al. Responsiveness to stimuli of bispectral index, middle latency auditory evoked potentials and clinical scales in critically ill children. Anaesthesia 2008;63:1296–301. Lamas A, López-Herce J, Sancho L, Mencía S, Carrillo A, Santiago MJ, et al. Assessing sedation in critically ill children by bispectral index, auditory-evoked potentials and clinical scales. Intensive Care Med 2008;34:2092–9. Lamas A, López-Herce J, Sancho L, Mencía S, Carrillo A, Santiago MJ, et al. Assessment of the level of sedation in children after cardiac surgery. Ann Thorac Surg 2009; 88(1):44–50. Aneja R, Heard AM, Fletcher JE, Heard CM. Sedation monitoring of children by the bispectral index in the pediatric intensive care unit. Pediatr Crit Care Med 2003;4: 60–4. Tonner PH, Wei C, Bein B, Weiler N, Paris A, Scholz J. Comparison of two bispectral index algorithms in monitoring sedation in postoperative intensive care patients. Crit Care Med 2005;33:580–4. Courtman SP, Wardurgh A, Petros AJ. Comparison of the bispectral index monitor with the COMFORT score in assessing level of sedation of critically ill children. Intensive Care Med 2003;29:2239–46. Triltsch AE, Nestmann G, Orawa H, Moshirzadeh M, Sander M, Grosse J, et al. Bispectral index versus COMFORT score to determine the level of sedation in paediatric intensive care unit patients: a prospective study. Crit Care 2005;9:9–17. Trope RM, Silver PC, Sagy M. Concomitant assessment of depth of sedation by changes in bispectral index and changes in autonomic variables (heart rate and/or BP) in pediatric critically ill patients receiving neuromuscular blockade. Chest 2005;128: 303–7. Storm H, Myre K, Rostrup M, Stokland O, Lien MD, Raeder JC. Skin conductance correlates with perioperative stress. Acta Anaesthesiol Scand 2002;46:887–95.