Sedation and analgesia in the PICU: many questions remain.
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Analgesia↗
Biomedical subjects
Monique van Dijk
Publications and source records attributed to Monique van Dijk.
Pain assessment: current status and challenges.
Neonatal pain assessment has received much attention over the past decade. Behavioural indicators of pain include facial action, body movement and tone, cry, state/sleep, and consolability. Physiological indicators of pain include increased heart rate, respiratory rate, and blood pressure, as well as decreased heart rate variability and oxygen desaturation. Pain assessment in neonates is difficult in neurologically compromised, chemically paralyzed, and non-responsive infants. Multiple pain assessment tools are summarized. Pain assessment and management protocols are delineated.
Biomarkers↗
Propofol pharmacokinetics and pharmacodynamics for depth of sedation in nonventilated infants after major craniofacial surgery.
BACKGROUND: To support safe and effective use of propofol in nonventilated children after major surgery, a model for propofol pharmacokinetics and pharmacodynamics is described. METHODS: After craniofacial surgery, 22 of the 44 evaluated infants (aged 3-17 months) in the pediatric intensive care unit received propofol (2-4 mg . kg-1 . h-1) during a median of 12.5 h, based on the COMFORT-Behavior score. COMFORT-Behavior scores and Bispectral Index values were recorded simultaneously. Population pharmacokinetic and pharmacodynamic modeling was performed using NONMEM V (GloboMax LLC, Hanover, MD). RESULTS: In the two-compartment model, body weight (median, 8.9 kg) was a significant covariate. Typical values were Cl = 0.70 . (BW/8.9)0.61 l/min, Vc = 18.8 l, Q = 0.35 l/min, and Vss = 146 l. In infants who received no sedative, depth of sedation was a function of baseline, postanesthesia effect (Emax model), and circadian night rhythm. In agitated infants, depth of sedation was best described by baseline, postanesthesia effect, and propofol effect (Emax model). The propofol concentration at half maximum effect was 1.76 mg/l (coefficient of variation = 47%) for the COMFORT-Behavior scale and 3.71 mg/l (coefficient of variation = 145%) for the Bispectral Index. CONCLUSIONS: Propofol clearance is two times higher in nonventilated healthy children than reported in the literature for ventilated children and adults. Based on the model, the authors advise a propofol dose of 30 mg/h in a 10-kg infant to achieve values of 12-14 on the COMFORT-Behavior scale and 70-75 on the Bispectral Index during the night. Wide pharmacodynamic variability emphasizes the importance of dose titration.
Craniosynostoses↗
The auditory evoked potential monitor: first data from infants outside the operation room.
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Acoustic Stimulation↗
Does neonatal surgery lead to increased pain sensitivity in later childhood?
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.
Analgesics, Opioid↗
The COMFORT Behavior Scale: a tool for assessing pain and sedation in infants.
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Analgesics↗
Pharmacodynamics of midazolam in pediatric intensive care patients.
The aim of the study was to study a possible pharmacokinetic-pharmacodynamic (PK-PD) relationship for midazolam in pediatric intensive care patients and to determine how adequate sedation could be reached using the COMFORT scale as sedation scale. Twenty-one pediatric intensive care patients (2 days to 17 years) received a midazolam infusion (0.05-0.4 mg/kg/h, 3.8 hours to 25 days). Sedation levels were determined using the COMFORT scale as well as plasma concentrations of midazolam and metabolites. An evident PK-PD relationship was not found. In 20 of the 21 patients midazolam dosing could be effectively titrated to the desired level of sedation, assessed by the COMFORT scale. Based on our findings that there is no relationship between pharmacokinetic parameters and pharmacodynamic outcome, we recommend that midazolam dosing should be titrated according to the desired clinical effect in combination with a validated assessment instrument, eg, the COMFORT scale.
Adolescent↗
Assessment of sedation levels in pediatric intensive care patients can be improved by using the COMFORT "behavior" scale.
OBJECTIVES: The original COMFORT scale, including both observational and physiologic items, has been validated for measuring distress in children admitted to a pediatric intensive care unit. However, physiologic variables are influenced by drugs given in the pediatric intensive care unit setting. The objectives of this study were to assess the usefulness of physiologic variables in judgment of sedation and to determine new cutoff points for the COMFORT "behavioral" scale (COMFORT-B), using only observational items. DESIGN: Prospective observational study. SETTING: Pediatric intensive care unit in a university hospital. PATIENTS: Seventy-eight patients admitted to the pediatric intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: COMFORT scores were obtained in this patient group. Similar to the original COMFORT scale validation, the expert opinion of nurses (Nurse Interpretation Score of Sedation) served to determine optimal cutoff scores for the COMFORT-B scale. A total of 843 combined COMFORT and Nurse Interpretation Score of Sedation scores were obtained in 78 patients. Cronbach's alpha for the COMFORT scale was .78, increasing to .84 when the physiologic items, blood pressure and heart rate, were excluded. COMFORT scores were significantly different for the three Nurse Interpretation Score of Sedation categories (Kruskal-Wallis, p < .001). According to the pediatric intensive care unit nurses, undersedation was present in 11% and oversedation in 3% of all observations. Cutoff points for the COMFORT-B scale were </=10 for oversedation and >/=23 for undersedation. The area in the COMFORT-B score between 11 and 22 does not adequately predict under- or oversedation, pointing to a need for supplemental observation. CONCLUSIONS: The COMFORT-B scale is a reliable alternative to the original COMFORT scale. The cutoff points of the COMFORT-B scale in conjunction with the Nurse Interpretation Score of Sedation facilitate the use of sedation algorithms on the pediatric intensive care unit.
Adolescent↗
Routine morphine infusion in preterm newborns who received ventilatory support: a randomized controlled trial.
CONTEXT: Newborns admitted to neonatal intensive care units (NICUs) undergo a variety of painful procedures and stressful events. Because the effect of continuous morphine infusion in preterm neonates has not been investigated systematically, there is confusion regarding whether morphine should be used routinely in this setting. OBJECTIVE: To evaluate the effects of continuous intravenous morphine infusion on pain responses, incidence of intraventricular hemorrhage (IVH), and poor neurologic outcome (severe IVH, periventricular leukomalacia, or death). DESIGN, SETTING, AND PATIENTS: A randomized, double-blind, placebo-controlled trial conducted between December 2000 and October 2002 in 2 level III NICUs in the Netherlands of 150 newborns who had received ventilatory support (inclusion criteria: postnatal age younger than 3 days and ventilation for less than 8 hours; exclusion criteria: severe asphyxia, severe IVH, major congenital malformations, and administration of neuromuscular blockers). INTERVENTIONS: Intravenous morphine (100 microg/kg and 10 microg/kg per hour) or placebo infusion was given for 7 days (or less because of clinical necessity in several cases). MAIN OUTCOME MEASURES: The analgesic effect of morphine, as assessed using validated scales; the effect of morphine on the incidence of IVH; and poor neurologic outcome. RESULTS: The analgesic effect did not differ between the morphine and placebo groups, judging from the following median (interquartile range) pain scores: Premature Infant Pain Profile, 10.1 (8.2-11.6) vs 10.0 (8.2-12.0) (P =.94); Neonatal Infant Pain Scale, 4.8 (3.7-6.0) vs 4.8 (3.2-6.0) (P =.58); and visual analog scale, 2.8 (2.0-3.9) vs 2.6 (1.8-4.3) (P =.14), respectively. Routine morphine infusion decreased the incidence of IVH (23% vs 40%, P =.04) but did not influence poor neurologic outcome (10% vs 16%, P =.66). In addition, analyses were adjusted for the use of additional open-label morphine (27% of morphine group vs 40% of placebo group, P =.10). CONCLUSIONS: Lack of a measurable analgesic effect and absence of a beneficial effect on poor neurologic outcome do not support the routine use of morphine infusions as a standard of care in preterm newborns who have received ventilatory support. Follow-up is needed to evaluate the long-term effects of morphine infusions on the neurobehavioral outcomes of prematurity.
Analgesics, Opioid↗
Postoperative pain in the neonate: age-related differences in morphine requirements and metabolism.
OBJECTIVE: To investigate age-related differences in morphine requirements and metabolism in full-term neonates. DESIGN AND SETTING: Randomized double-blind study in the pediatric surgical intensive care unit. PATIENTS: Sixty-eight neonates (52 aged under 7 days, 16 aged 7 day or older) following major surgery. INTERVENTIONS: After surgery patients were randomly assigned to continuous morphine (10 micro g/kg per hour) or intermittent morphine (30 micro g/kg per 3 hours). Additional morphine was administered on guidance of pain scores. MEASUREMENTS AND RESULTS: Pain was measured by the Comfort behavioral scale and visual analogue scale. Morphine and morphine-6-glucuronide (M6G) plasma concentrations were determined before and 0, 6, 12, and 24 h after surgery. The younger neonates differed significantly from the older neonates in morphine requirement (median 10 vs. 10.8 micro g/kg per hour), morphine plasma concentration [23.0 vs. 15.3 ng/ml), and M6G/morphine ratio (0.6 vs. 1.5). Pain scores did not differ between age groups or morphine treatment groups. Neonates who were mechanically ventilated longer than 24 h had significantly higher morphine plasma concentrations than the spontaneously breathing neonates 12 and 24 h after surgery (29.1 vs. 13.1 ng/ml and 26.9 vs. 12.0 ng/ml, respectively). Morphine plasma concentrations were not correlated with analgesia or respiratory depression. Five neonates (intermittent morphine) showed respiratory insufficiency; however, the difference between the groups was not significant. CONCLUSIONS: Neonates aged 7 days or younger require significantly less morphine postoperatively than older neonates. The two morphine regimens (continuous, intermittent) were equally effective and safe. Mechanical ventilation decreases morphine metabolism and clearance.
Age Factors↗
Do we still hurt newborn babies? A prospective study of procedural pain and analgesia in neonates.
BACKGROUND: Despite an increasing awareness regarding pain management in neonates and the availability of published guidelines for the treatment of procedural pain, preterm neonates experience pain leading to short- and long-term detrimental effects. OBJECTIVE: To assess the frequency of use of analgesics in invasive procedures in neonates and the associated pain burden in this population. METHODS: For 151 neonates, we prospectively recorded all painful procedures, including the number of attempts required, and analgesic therapy used during the first 14 days of neonatal intensive care unit admission. These data were linked to estimates of the pain of each procedure, obtained from the opinions of experienced clinicians. RESULTS: On average, each neonate was subjected to a mean +/- SD of 14 +/- 4 procedures per day. The highest exposure to painful procedures occurred during the first day of admission, and most procedures (63.6%) consisted of suctioning. Many procedures (26 of 31 listed on a questionnaire) were estimated to be painful (pain scores >4 on a 10-point scale). Preemptive analgesic therapy was provided to fewer than 35% of neonates per study day, while 39.7% of the neonates did not receive any analgesic therapy in the neonatal intensive care unit. CONCLUSIONS: Clinicians estimated that most neonatal intensive care unit procedures are painful, but only a third of the neonates received appropriate analgesic therapy. Despite the accumulating evidence that neonatal procedural pain is harmful, analgesic treatment for painful procedures is limited. Systematic approaches are required to reduce the occurrence of pain and to improve the analgesic treatment of repetitive pain in neonates.
Analgesics↗
Are postoperative pain instruments useful for specific groups of vulnerable infants?
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.
Child, Preschool↗
Efficacy of continuous versus intermittent morphine administration after major surgery in 0-3-year-old infants; a double-blind randomized controlled trial.
A randomized double-blind clinical trial compared the efficacy of 10 microg/kg/h morphine continuous intravenous infusion (CM) with that of 30 microg/kg morphine (IM) every 3h after major abdominal or thoracic surgery, in 181 infants aged 0-3 years. Efficacy was assessed by the caregiving nurses with the COMFORT 'behavior' and a visual analogue scale (VAS) for pain, every 3h in the first 24h after surgery. Random regression modeling was used to simultaneously estimate the effect of randomized group assignment, actual morphine dose (protocol dosage plus extra morphine when required), age category, surgical stress, and the time-varying covariate mechanical ventilation on COMFORT 'behavior' and the observational VAS rated pain, respectively. Overall, no statistical differences were found between CM and IM morphine administration in reducing postoperative pain. A significant interaction effect of condition with age category showed that the CM assignment was favorable for the oldest age category (1-3 years old). The greatest differences in pain response and actual morphine dose were between neonates and infants aged 1-6 months, with lower pain response in neonates who were on average satisfied with the protocol dosage of 10 microg/kg/h. Surgical stress and mechanical ventilation were not related to postoperative pain or morphine doses, leaving the inter-individual differences in pain response and morphine requirement largely unexplained.
Age Factors↗
Observational visual analog scale in pediatric pain assessment: useful tool or good riddance?
DESIGN: The authors reviewed the available pediatric pain literature and selected those studies that reported quantitative information on the reliability and validity of, and the optimal cutoff points for, the visual analog scale (VAS) when used as an observational pediatric pain tool. RESULTS: Available psychometric findings concerning the observational VAS (VAS obs ) are limited. The estimated interrater reliability of the VAS (obs) from 9 studies ranged from 0.36 to 0.91. The correlation between self-report and the VAS (obs) was variable and ranged 0.23 to 0.83 in 6 studies. The concurrent validity of the VAS (obs) and other pain instruments ranged from 0.42 to 0.86. CONCLUSIONS: Further psychometric testing needs to be conducted on intraobserver reliability, responsiveness, and optimal cutoff points. Future research may guide the choice between VAS (obs) and the numerous behavioral pain instruments.
Adolescent↗
Observation scales for pain assessment in older adults with cognitive impairments or communication difficulties.
BACKGROUND: Several pain observation scales have been developed to accurately assess and manage pain in older adults with severe cognitive impairments, communication difficulties, or both. OBJECTIVE: To review relevant pain observation scales and the psychometric qualities of these scales. METHODS: The literature was searched for articles reporting the use of a pain observation scale in an empirical study and describing psychometric properties in older adults with cognitive impairments, communication difficulties, or both. RESULTS: Thirteen pain observation scales were included. Scales differed in numbers of items, types of categories, and psychometric properties. Facial expression, vocalization, motor behavior, and social behavior or mood are categories present in most of the scales. In terms of reliability and validity, however, most studies are too limited or incomplete to allow definite conclusions to be drawn about usefulness in daily practice. DISCUSSION: As different methods of evaluating reliability and validity were used, and different aims (e.g., type of pain) were pursued, the available scales cannot be compared easily. Nevertheless, a few are promising, given preliminary results. These should be examined further on psychometric properties and usefulness in different populations because optimal pain assessment is necessary for efficient and effective pain treatment.
Aged↗