Tom G. de Leeuw

Effect of intravenous paracetamol on postoperative morphine requirements in neonates and infants undergoing major noncardiac surgery: A randomized controlled trial

IMPORTANCE Continuous morphine infusion as standard postoperative analgesic therapy in young infants is associated with unwanted adverse effects such as respiratory depression. OBJECTIVE To determine whether intravenous paracetamol (acetaminophen) would significantly (>30%) reduce morphine requirements in neonates and infants after major surgery. DESIGN, SETTING, AND PATIENTS Single-center, randomized, double-blind study conducted in a level 3 pediatric intensive care unit in Rotterdam, The Netherlands. Patients were 71 neonates or infants younger than 1 year undergoing major thoracic (noncardiac) or abdominal surgery between March 2008 and July 2010, with follow-up of 48 hours. INTERVENTIONS All patients received a loading dose of morphine 30 minutes before the end of surgery, followed by continuous morphine or intermittent intravenous paracetamol up to 48 hours postsurgery. Infants in both study groups received morphine (boluses and/or continuous infusion) as rescue medication on the guidance of the validated pain assessment instruments. MAIN OUTCOME MEASURES Primary outcome was cumulative morphine dose (study and rescue dose). Secondary outcomes were pain scores and morphine-related adverse effects. RESULTS The cumulative median morphine dose in the first 48 hours postoperatively was 121 (interquartile range, 99-264) μg/kg in the paracetamol group (n = 33) and 357 (interquartile range, 220-605) μg/kg in the morphine group (n = 38), P < .001, with a between-group difference that was 66% (95% CI, 34%-109%) lower in the paracetamol group. Pain scores and adverse effects were not significantly different between groups. CONCLUSION AND RELEVANCE Among infants undergoing major surgery, postoperative use of intermittent intravenous paracetamol compared with continuous morphine resulted in a lower cumulative morphine dose over 48 hours. TRIAL REGISTRATION trialregister.nl Identifier: NTR1438.

Lower bispectral index values in children who are intellectually disabled.

BACKGROUND: Very few data are available on the use of bispectral index (BIS) monitoring in children who are intellectually disabled. Epileptiform electroencephalogram activity, underlying cerebral pathology, or anticonvulsant/spasmolytic therapy might influence BIS monitoring. Our aim in this exploratory study was to first compare BIS values at 4 different stages of anesthesia between intellectually disabled children and controls. Our second aim was to investigate the discriminative properties of BIS between consciousness and unconsciousness for intellectually disabled children and for controls. METHODS: Eighteen intellectually disabled children and 35 control children, aged 2–13 yr, were included. BIS values, landmark events, and standard monitoring values of vital functions were recorded throughout the whole procedure. The performance of BIS in distinguishing between a conscious and unconscious state was assessed from receiver operating characteristic curves. RESULTS: Median (interquartile range) BIS values for the intellectually disabled group were significantly lower than those for controls in the awake state (72 [48–77] vs 97 [84–98], P < 0.001), during stable intraoperative anesthesia (34 [21–45] vs 43 [33–52], P = 0.02), and during return of consciousness (59 [36–68] vs 73 [64–78], P = 0.009). The discriminative properties of the BIS monitor for the state of consciousness were comparable between the 2 groups according to the receiver operating characteristic curves. Nevertheless, the optimal cutoff BIS value for discrimination between conscious and unconscious state was 28 points lower for the intellectually disabled group. CONCLUSIONS: We advise anesthesiologists to be alert to possible lower BIS values in intellectually disabled children. There is a risk that they will inadvertently misinterpret the state of consciousness in intellectually disabled children. New multicenter studies must find the optimal manner of evaluating (un)consciousness in intellectually disabled patients with documented and confirmed specific etiologies of their intellectual disability.

A Comparison in Adolescents of Composite Auditory Evoked Potential Index and Bispectral Index During Propofol-Remifentanil Anesthesia for Scoliosis Surgery with Intraoperative Wake-Up Test

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparison of Bispectral Index and Composite Auditory Evoked Potential Index for Monitoring Depth of Hypnosis in Children

Background: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. Methods: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. Results: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. Conclusions:BIS and cAAI were comparable indicators of depth of hypnosis in children. Both indices, however, showed considerable overlap for different clinical conditions.

Pain management in intellectually disabled children: a survey of perceptions and current practices among Dutch anesthesiologists

Background:  Intellectually disabled children are more likely to undergo surgical interventions and almost all have comorbidities that need to be managed. Compared with controls, intellectually disabled children tend to receive less intraoperative analgesia and fewer of them are assessed for postoperative pain.

Extremely low preanesthetic BIS values in two children with West syndrome and lissencephaly

partial surgical removal of cervicofacial lymphangyomas. Arch Otolaryngol Head Neck Surg 1999; 125: 643–648. 10 Thompson AE. Issues in airway management in infants and children. Respir Care 1999; 44: 650. 11 Berkenbosch JW, Graff GR, Stark JM et al. Use of a remifentanil–propofol mixture for pediatric flexible fiberoptic bronchoscopy sedation. Pediatr Anesth 2004; 14: 941–946. 12 Reinoso-Barbero F, Castro LE. Influencia de la edad pediátrica en la técnica de anestesia basada en la analgesia con remifentanilo. Rev Esp Anestesiol Reanim 2004; 51: 12–19. 13 Vidal MA, Velázquez A, Morgado I et al. Sedación con remifentanilo para una traqueostomı́a en un paciente pediátrico. Rev Esp Anestesiol Reanim 2004; 51: 600–603. 14 American Society of Anesthesiologist Task Force on Management of the Difficult Airway. Practice guidelines for management of the difficult airway: an update report by the American Society of Anesthesiologist Task Force of Management of Difficult Airway. Anesthesiology 2003; 98: 1269–1277. 15 Ovassapian A. Fiberoptic Airway Endoscopy in Anesthesia and Critical Care, 1st edn. New York: Raven, 1990: 149–162. 16 Omote K, Kawamata T, Imaizumi H et al. Case of Cowden’s disease that caused airway obstruction during induction of anesthesia. Anesthesiology 1999; 91: 1537–1540. 17 Benumof JL. Laryngeal mask airway and the ASA difficult airway algorithm. Anesthesiology 1996; 684: 86.

Pain in Intellectually Disabled Children: Towards Evidence-Based Pharmacotherapy?

This critical opinion article deals with the challenges of finding the most effective pharmacotherapeutic options for the management of pain in intellectually disabled children and provides recommendations for clinical practice and research. Intellectual disability can be caused by a wide variety of underlying diseases and may be associated with congenital anomalies such as cardiac defects, small-bowel obstructions or limb abnormalities as well as with comorbidities such as scoliosis, gastro-esophageal reflux disease, spasticity, and epilepsy. These conditions themselves or any necessary surgical interventions are sources of pain. Epilepsy often requires chronic pharmacological treatment with antiepileptic drugs. These antiepileptic drugs can potentially cause drug–drug interactions with analgesic drugs. It is unfortunate that children with intellectual disabilities often cannot communicate pain to caregivers. Although these children are at high risk of experiencing pain, researchers nevertheless often have to exclude them from trials on pain management because of ethical considerations. We therefore make a plea for prescribers, researchers, patient organizations, pharmaceutical companies, and policy makers to study evidence-based, safe and effective pharmacotherapy in these children through properly designed studies. In the meantime, parents and clinicians must resort to validated pain assessment tools such as the revised FLACC scale.