[Show abstract][Hide abstract] ABSTRACT: The electroencephalogram-derived Bispectral Index (BIS), and the composite A-line ARX index (cAAI), derived from the electroencephalogram and auditory evoked potentials, have been promoted as anesthesia depth monitors. Using an intraoperative wake-up test, we compared the performance of both indices in distinguishing different hypnotic states, as evaluated by the University of Michigan Sedation Scale, in children and adolescents during propofol-remifentanil anesthesia for scoliosis surgery. Postoperative explicit recall was also evaluated.
Twenty patients (aged 10-20 yr) were enrolled. Prediction probabilities were calculated for induction, wake-up test, and emergence. BIS and cAAI were compared at the start of the wake-up test, at purposeful movement to command, and after the patient was reanesthetized. During the wake-up test, patients were instructed to remember a color, and were then interviewed for explicit recall.
Prediction probabilities of BIS and cAAI for induction were 0.82 and 0.63 (P < 0.001), for the wake-up test, 0.78 and 0.79 (P < 0.001), and 0.74 and 0.78 for emergence (P < 0.001). During the wake-up test, a significant increase in mean BIS and cAAI (P < 0.05) was demonstrated at purposeful movement, followed by a significant decline after reintroduction of anesthesia.
During induction, BIS performed better than cAAI. Although cAAI was statistically a better discriminator for the level of consciousness during the wake-up test and emergence, these differences do not appear to be clinically meaningful. Both indices increased during the wake-up test, indicating a higher level of consciousness. No explicit recall was demonstrated.
Full-text · Article · Nov 2008 · Anesthesia and analgesia
[Show abstract][Hide abstract] ABSTRACT: Measurement of pain in pre-verbal infants is complex. Until now, pain behavior has mainly been assessed intermittently using observational tools. Therefore, we determined the feasibility of long-term, objective and continuous measurement of peripheral motor parameters through body-fixed sensors to discriminate between pain and no pain in hospitalized pre-verbal infants. Two pain modes were studied: for procedural pain 10 measurements were performed before, during and after routine heel lances in 9 infants (age range infants: 5-175 days), and for post-operative pain 14 infants (age range 45-400 days) were measured for prolonged periods (mean 7h) using the validated COMFORT-behavior scale as reference method. Several peripheral motor parameters were studied: three body part activity parameters derived from acceleration sensors attached to one arm and both legs, and two muscle activity parameters derived from electromyographic (EMG) sensors attached to wrist flexor and extensor muscles. Results showed that the accelerometry-based parameters legs activity and overall extremity activity (i.e. mean of arm and legs) were significantly higher during heel lance than before or after lance (p0.001), whereas arm activity accelerometry data and wrist muscle activity EMG data showed no significant change. For the post-operative pain measurements, relationships were found between accelerometry-based overall extremity activity and COMFORT-behavior (r=0.76, p<0.001), and between EMG-based wrist flexor activity and COMFORT-behavior (r=0.55, p<0.001, for a subgroup of 7 infants). We conclude that long-term, objective and continuous measurement of peripheral motor parameters is feasible, has high potential, and is promising to assess pain in pre-verbal hospitalized infants.
[Show abstract][Hide abstract] ABSTRACT: In pediatric patients, the Bispectral Index (BIS), derived from the electroencephalogram, and the composite A-Line autoregressive index (cAAI), derived from auditory evoked potentials and the electroencephalogram, have been used as measurements of depth of hypnosis during anesthesia. The performance and reliability of BIS and cAAI in distinguishing different hypnotic states in children, as evaluated with the University of Michigan Sedation Scale, were compared.
Thirty-nine children (aged 2-16 yr) scheduled to undergo elective inguinal hernia surgery were studied. For all patients, standardized anesthesia was used. Prediction probabilities of BIS and cAAI versus the University of Michigan Sedation Scale and sensitivity/specificity were calculated.
Prediction probabilities for BIS and cAAI during induction were 0.84 for both and during emergence were 0.75 and 0.74, respectively. At loss of consciousness, the median BIS remained unaltered (94 to 90; not significant), whereas cAAI values decreased (60 to 43; P < 0.001). During emergence, median BIS and cAAI increased from 51 to 74 (P < 0.003) and from 46 to 58 (P < 0.001), respectively. With respect to indicate consciousness or unconsciousness, 100% sensitivity was reached at cutoff values of 17 for BIS and 12 for cAAI. One hundred percent specificity was associated with a BIS of 71 and a cAAI of 60. To ascertain consciousness, BIS values greater than 78 and cAAI values above 52 were required.
BIS and cAAI were comparable indicators of depth of hypnosis in children. Both indices, however, showed considerable overlap for different clinical conditions.
[Show abstract][Hide abstract] ABSTRACT: The low tactile threshold in preterm infants when they are in the neonatal intensive care unit (NICU), while their physiological systems are unstable and immature, potentially renders them more vulnerable to the effects of repeated invasive procedures. There is a small but growing literature on pain and tactile responsivity following procedural pain in the NICU, or early surgery. Long-term effects of repeated pain in the neonatal period on neurodevelopment await further research. However, there are multiple sources of stress in the NICU, which contribute to inducing high overall 'allostatic load', therefore determining specific effects of neonatal pain in human infants is challenging.
Full-text · Article · Sep 2006 · Seminars in Fetal and Neonatal Medicine
[Show abstract][Hide abstract] ABSTRACT: To examine morphine metabolite serum concentrations in neonates undergoing venoarterial extra corporeal membrane oxygenation (ECMO) and to quantify clearance differences between these neonates and those subjected to noncardiac major surgery.
This was an observational study in level III referral centre. Fourteen neonates (< 7 days old) undergoing ECMO were included. Morphine and concomitant medications were given by protocol, adapted to the clinical conditions of the neonates. Pharmacokinetic findings were compared with those from a previous study in infants after noncardiac major surgery. Nonlinear mixed-effect modelling was used. Parameter estimates were standardised to a 70 kg person using allometric modeling
Morphine-3-glucuronide (M3G) was the predominant metabolite. Formation clearance to M3G at the start of ECMO on day 1 was lower than those in postoperative children, but matured more rapidly. After 10 days formation clearances of M3G in neonates on ECMO equalled those of postoperative children. Higher ECMO flows were associated with reduced formation clearances. Elimination clearances of M3G, but not morphine-6-glucuronide (M6G), were lower in the ECMO neonates; this was attributable to reduced renal clearance. These elimination clearances were correlated positively with ECMO flow and negatively with dopamine dose. Haemofiltration cleared M3G and M6G, but not morphine.
Formation clearance to M3G, the predominant metabolite, is reduced during the first 10 days of ECMO. Elimination clearance of M3G and M6G is related to creatinine clearance. ECMO flow had a small effect on metabolite clearance. Higher flows were associated with decreased formation clearances, possibly reflecting illness severity. Dopamine dose reflected decreased renal clearance.
No preview · Article · Feb 2006 · Clinical Pharmacokinetics
[Show abstract][Hide abstract] ABSTRACT: Research in child subjects requires parental permission. We examined whether parental authorization of involvement in a clinical study is influenced by the child's severity of illness at the time of the consent decision.
Observational study in a multidisciplinary tertiary pediatric and neonatal intensive care.
Parents of 421 children (age range from preterm to 18 years) were asked to consent for participation in a study focusing on measuring their child's nutritional status within 24 h after admission to the ICU. Over 20% of the parents (n=88) refused consent, most of them because they expected the study to be too burdensome for their child.
Patient and disease characteristics were comparable in the children for whom consent had or had not been obtained. A higher illness severity score did not decrease the probability of obtaining informed consent, but parents of children with a history of disease were 3.2 times less likely to consent.
Parents of children with higher illness severity scores are not more likely to decline permission to include their child in clinical observational research on the ICU. History of disease and subjectively perceived burden to the child are important factors that must be considered.
Full-text · Article · Jul 2005 · Intensive Care Medicine
[Show abstract][Hide abstract] ABSTRACT: To evaluate over a 5-yr period the feasibility and tolerance of a protocol of routine enteral nutrition in neonates requiring extracorporeal membrane oxygenation (ECMO).
Retrospective medical chart review.
Level III children's hospital, pediatric surgical intensive care unit.
Neonates treated with venoarterial ECMO (VA-ECMO) between January 1997 and January 2002. Patients with congenital diaphragmatic hernia were excluded.
Charts of all neonates treated with VA-ECMO were reviewed. Feasibility was evaluated by recording the time period needed for enteral nutrition to reach 40% of total fluid intake; tolerance was evaluated by reviewing data on enteral nutrition related morbidity. Sixty-seven of the 77 eligible patients received enteral feeding during ECMO. Thirty-six of these patients (54%) received 40% of total fluid intake as enteral nutrition within a median of 3 (range, 2-4) days. Over the years there was a trend toward an increasing usage of enteral nutrition from 71% to 94% (p = .07). Enteral nutrition was temporarily discontinued in 16 patients, with 14 showing gastric retentions, one showing discomfort, and one showing aspiration. Symptoms of bilious vomiting, blood-stained stool, or abdominal distention were not present.
Neonates on ECMO in this series tolerated enteral feeding well and did not show serious adverse effects. Overall, it is our experience that routine use of enteral feeding in critically ill neonates on VA-ECMO is feasible.
No preview · Article · Jun 2005 · Pediatric Critical Care Medicine
[Show abstract][Hide abstract] ABSTRACT: Does pain or tissue damage in early life lead to hyperalgesia persisting into childhood? We performed a cross-sectional study in 164 infants to investigate whether major surgery within the first 3 months of life increases pain sensitivity to subsequent surgery and to elucidate whether subsequent surgery in the same dermatome or in a different dermatome leads to differences in pain sensitivity. All infants received standard intraoperative and postoperative pain management, with rescue analgesia guided by a treatment algorithm. Differences in pain sensitivity during surgery were assessed by the intraoperative fentanyl intake and by (nor)epinephrine plasma concentrations. Differences in postoperative pain sensitivity were assessed by the observational pain measures COMFORT and VAS, and by morphine intake and (nor)epinephrine plasma concentrations. Infants previously operated upon in the same dermatome needed more intraoperative fentanyl, had higher COMFORT and VAS scores, had greater (nor)epinephrine plasma concentrations, and needed also more morphine than did infants with no prior surgery. In contrast, infants who previously underwent surgery in another dermatome had only significant higher postoperative analgesic requirements and norepinephrine plasma concentrations in comparison with infants with no prior surgery. These preliminary differences may indicate the occurrence of spinal and supraspinal changes following neonatal surgery. We conclude that the long-term consequences of surgery in early infancy are greater in areas of prior tissue damage and that these effects may portend limited clinical but important neurobiological differences.
[Show abstract][Hide abstract] ABSTRACT: To study morphine pharmacokinetics in neonates undergoing venoarterial ECMO and to quantify differences between these neonates and neonates subjected to noncardiac major surgery.
Observational study in a level III referral center.
Pharmacokinetic estimates from 14 neonates undergoing ECMO were compared with findings from a previous study in 0- to 3-year-olds after noncardiac major surgery using a nonlinear mixed effect model. A one-compartment linear disposition model with zero-order input (infusion) and first-order elimination was used to describe all data.
Clearance in neonates (age <7 days) at the start of ECMO (2.2 l per hour per 70 kg) was lower than that in postoperative neonates (10.5 l per hour per 70 kg) but increased rapidly (maturation half-life 30 and 70 days, respectively) and equaled that of the postoperative group after 14 days. Clearance was affected by size and age only. Exchange transfusion, when used, contributed only 1.1% (CV 46%) of total clearance. Distribution volume increased with age and was 2.5 times (CV 102%) greater in ECMO children than in postoperative children. The between-subject variability values for volume of distribution and clearance were 49.4% and 38.7%. Weight and age information explained 83% of the overall clearance variability and 60% of overall distribution volume variability.
Morphine clearance is reduced in infants requiring ECMO, possibly reflecting severity of illness. Clearance maturation on ECMO is rapid and normalizes within 2 weeks. Initial morphine dosing may be guided by age and weight, but clearance and distribution volume changes (and their variability) during prolonged ECMO suggests that morphine therapy should be subsequently guided by clinical monitoring.
No preview · Article · Mar 2005 · Intensive Care Medicine
[Show abstract][Hide abstract] ABSTRACT: Objective: The objectives of this study were to: (1) evaluate the validity of the Neonatal Facial Coding System (NFCS) for assessment of postoperative pain and (2) explore whether the number of NFCS facial actions could be reduced for assessing postoperative pain. Design: Prospective, observational study. Patients: Thirty-seven children (0-18 months old) undergoing major abdominal or thoracic surgery. Outcome Measures: The outcome measures were the NFCS, COMFORT "behavior" scale, and a Visual Analog Scale (VAS), as well as heart rate, blood pressure, and catecholamine and morphine plasma concentrations. At 3-hour intervals during the first 24 hours after surgery, nurses recorded the children's heart rates and blood pressures and assigned COMFORT "behavior" and VAS scores. Simultaneously we videotaped the children's faces for NFCS coding. Plasma concentrations of catecholamine, morphine, and its metabolite M6G were determined just after surgery, and at 6, 12, and 24 hours postoperatively. Results: All 10 NFCS items were combined into a single index of pain. This index was significantly associated with COMFORT "behavior" and VAS scores, and with heart rate and blood pressure, but not with catecholamine, morphine, or M6G plasma concentrations. Multidimensional scaling revealed that brow bulge, eye squeeze, nasolabial furrow, horizontal mouth stretch, and taut tongue could be combined into a reduced measure of pain. The remaining items were not interrelated. This reduced NFCS measure was also significantly associated with COMFORT "behavior" and VAS scores, and with heart rate and blood pressure, but not with the catecholamine, morphine, or M6G plasma concentrations. Conclusion: This study demonstrates that the NFCS is a reliable, feasible, and valid tool for assessing postoperative pain. The reduction of the NFCS to 5 items increases the specificity for pain assessment without reducing the sensitivity and validity for detecting changes in pain.
No preview · Article · Nov 2003 · Clinical Journal of Pain
[Show abstract][Hide abstract] ABSTRACT: Pain exposure during early infancy affects the pain perception beyond infancy into childhood. The objective of this study was to examine whether major surgery within the first 3 months of life in combination with preemptive analgesia alters pain responses to immunization at 14 or 45 months and to assess whether these alterations are greater in toddlers with a larger number of negative hospital experiences.
Two groups of 50 toddlers each were compared: index group and control group. All index toddlers had participated within the first 3 months of their life in a randomized, clinical trial that evaluated the efficacy of preemptive morphine administration for postoperative analgesia. The controls were matched by type of immunization and community health care pediatrician. Pain reactions were recorded at routine immunization at either 14 (measles-mumps-rubella immunization) or 45 months (diphtheria-tetanus-trivalent polio immunization) of age. Outcome measures were facial reaction, coded by the Maximum Discriminative Facial Movement Coding System; heart rate (HR); and cortisol saliva concentration. Negative hospital experiences included number of operations requiring postoperative morphine administration, cumulative Therapeutic Intervention Scoring System scores, and length of stay in the intensive care unit or total hospitalization days.
No differences were found between the index and control groups in the facial display of pain, anger, or sadness or in physiologic parameters such as HR and cortisol concentrations. Intragroup analyses of the index group showed that after measles-mumps-rubella vaccination, the number of negative hospital experiences correlated positively with the facial responsiveness and negatively with HR responses. No effect was seen after diphtheria-tetanus-trivalent polio immunization.
Major surgery in combination with preemptive analgesia within the first months of life does not alter pain response to subsequent pain exposure in childhood. Greater exposure to early hospitalization influences the pain responses after prolonged time. These responses, however, diminish after a prolonged period of nonexposure.
[Show abstract][Hide abstract] ABSTRACT: The objectives of this study were to: (1). evaluate the validity of the Neonatal Facial Coding System (NFCS) for assessment of postoperative pain and (2). explore whether the number of NFCS facial actions could be reduced for assessing postoperative pain.
Prospective, observational study.
Thirty-seven children (0-18 months old) undergoing major abdominal or thoracic surgery.
The outcome measures were the NFCS, COMFORT "behavior" scale, and a Visual Analog Scale (VAS), as well as heart rate, blood pressure, and catecholamine and morphine plasma concentrations. At 3-hour intervals during the first 24 hours after surgery, nurses recorded the children's heart rates and blood pressures and assigned COMFORT "behavior" and VAS scores. Simultaneously we videotaped the children's faces for NFCS coding. Plasma concentrations of catecholamine, morphine, and its metabolite M6G were determined just after surgery, and at 6, 12, and 24 hours postoperatively.
All 10 NFCS items were combined into a single index of pain. This index was significantly associated with COMFORT "behavior" and VAS scores, and with heart rate and blood pressure, but not with catecholamine, morphine, or M6G plasma concentrations. Multidimensional scaling revealed that brow bulge, eye squeeze, nasolabial furrow, horizontal mouth stretch, and taut tongue could be combined into a reduced measure of pain. The remaining items were not interrelated. This reduced NFCS measure was also significantly associated with COMFORT "behavior" and VAS scores, and with heart rate and blood pressure, but not with the catecholamine, morphine, or M6G plasma concentrations.
This study demonstrates that the NFCS is a reliable, feasible, and valid tool for assessing postoperative pain. The reduction of the NFCS to 5 items increases the specificity for pain assessment without reducing the sensitivity and validity for detecting changes in pain.
Full-text · Article · Jan 2003 · Clinical Journal of Pain
[Show abstract][Hide abstract] ABSTRACT: Based on the authors' review of the literature on pediatric postoperative pain assessment with special attention to groups of vulnerable infants, this article (1) reports on type of surgery and its relationship to postoperative pain intensity; (2) reviews the characteristics of existing postoperative pain instruments for neonates, infants, and toddlers; (3) discusses timing, duration, and who should assess postoperative pain; (4) reviews the specific literature on pain assessment in critically ill infants, including the extremely low birth weight and the cognitively and/or neurologically impaired infant, and (5) discusses the role of parents in postoperative pain assessment. Postoperative pain instruments are useful for specific groups of vulnerable infants, but it is important that in addition to the valuable scoring of pain, common sense is used and factors such as developmental stage, temperament and personality, number of previous painful experiences, anxiety, and environmental factors are taken into account.
Full-text · Article · Oct 2002 · Clinics in Perinatology