Navil F. Sethna

Core outcome domains and measures for pediatric acute and chronic/recurrent pain clinical trials: PedIMMPACT recommendations

UNLABELLED Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 26 professionals from academia, governmental agencies, and the pharmaceutical industry participated in a 2-stage Delphi poll and a consensus meeting that identified core outcome domains and measures that should be considered in clinical trials of treatments for acute and chronic pain in children and adolescents. Consensus was refined by consultation with the international pediatric pain community through announcement of our recommendations on the Pediatric Pain List and inviting and incorporating comments from external sources. There was consensus that investigators conducting pediatric acute pain clinical trials should consider assessing outcomes in pain intensity; global judgment of satisfaction with treatment; symptoms and adverse events; physical recovery; emotional response; and economic factors. There was also agreement that investigators conducting pediatric clinical trials in chronic and recurrent pain should consider assessing outcomes in pain intensity; physical functioning; emotional functioning; role functioning; symptoms and adverse events; global judgment of satisfaction with treatment; sleep; and economic factors. Specific measures or measurement strategies were recommended for different age groups for each domain. PERSPECTIVE Based on systematic review and consensus of experts, core domains and measures for clinical trials to treat pain in children and adolescents were defined. This will assist in comparison and pooling of data and promote evidence-based treatment, encourage complete reporting of outcomes, simplify the review of proposals and manuscripts, and facilitate clinicians making informed decisions regarding treatment.

Patient-controlled analgesia in children and adolescents: A randomized, prospective comparison with intramuscular administration of morphine for postoperative analgesia

A randomized, prospective trial of patient-controlled analgesia (PCA), that is, a method of analgesia administration involving a computer-driven pump activated by patients to receive small doses within defined limits was performed in 82 children and adolescents after major orthopedic surgery to compare (1) intramuscularly administered morphine, (2) PCA morphine and (3) PCA morphine with a low-dose continuous morphine infusion (PCA-plus). Patients receiving PCA and PCA-plus had lower pain scores and greater satisfaction than patients receiving intramuscularly administered morphine. The three groups used equal amounts of morphine and most measures of recovery were identical in the groups. In particular, PCA and PCA-plus did not increase the incidence of opioid-related complications, and patients receiving PCA-plus were less sedated than patients receiving intramuscular therapy. We conclude that PCA and PCA-plus are safe and effective methods of pain relief in children and adolescents after orthopedic surgery, are better accepted than intramuscular injections, and do not increase perioperative morbidity.

Tranexamic Acid Reduces Intraoperative Blood Loss in Pediatric Patients Undergoing Scoliosis Surgery

Background: Excessive bleeding often occurs during pediatric scoliosis surgery and is attributed to numerous factors, including accelerated fibrinolysis. The authors hypothesized that administration of tranexamic acid would reduce bleeding and transfusion requirements during scoliosis surgery. Methods: Forty-four patients scheduled to undergo elective spinal fusion were randomly assigned to receive either 100 mg/kg tranexamic acid before incision followed by an infusion of 10 mg · kg−1 · h−1 during surgery (tranexamic acid group) or 0.9% saline (placebo group). General anesthesia was administered according to a standard protocol. Blood loss, transfusion requirements, coagulation parameters, and complications were assessed. Results: In the tranexamic acid group, blood loss was reduced by 41% compared with placebo (1,230 ± 535 vs. 2,085 ± 1,188 ml; P < 0.01). The amount of blood transfused did not differ between groups (615 ± 460 vs. 940 ± 718 ml; P = 0.08). Administration of tranexamic acid was a multivariate predictor of blood loss, as was American Society of Anesthesiologists physical status and preoperative platelet count. No apparent adverse drug effects occurred in any patient. Conclusion: Intraoperative administration of tranexamic acid significantly reduces blood loss during spinal surgery in children with scoliosis.

REGIONAL ANESTHESIA AND ANALGESIA

Local and regional anesthetic techniques have a significant but limited place in the practice of infant pain control. In certain clinical circumstances, regional anesthetic techniques presumably afford many of the same advantages for the pediatric patient as in the adult patient. However, there are few controlled clinical trials on the advantages and adverse effects compared with conventional analgesic strategies. This article discusses the clinical application, effectiveness, safety, and outcomes of the available local and regional anesthetic techniques for control of postoperative and procedure-related pain in neonates and infants.

Efficacy of Tranexamic Acid in Pediatric Craniosynostosis Surgery: A Double-blind, Placebo-controlled Trial

Background:Extensive blood loss is common in pediatric craniosynostosis reconstruction surgery. Tranexamic acid (TXA) is increasingly used to reduce perioperative blood loss in various settings, but data on its efficacy are limited in children. The purpose of this randomized, double-blind, placebo-controlled, parallel trial was to evaluate the efficacy of TXA in pediatric craniosynostosis correction surgery. The primary and secondary outcome variables were reduction in perioperative blood loss and reduction in blood transfusion, respectively. Methods:Forty-three children, ages 2 months to 6 yr, received either placebo or TXA in a loading dose of 50 mg·kg−1, followed by an infusion of 5 mg·kg−1·h−1 during surgery. TXA plasma concentrations were measured. Results:The TXA group had significantly lower perioperative mean blood loss (65 vs. 119 ml·kg−1, P < 0.001) and lower perioperative mean blood transfusion (33 vs. 56 ml· kg−1, P = 0.006) compared to the placebo group. The mean difference between the TXA and placebo groups for total blood loss was 54 ml·kg−1 (95% CI for the difference, 23–84 ml·kg−1) and for packed erythrocytes transfused was 23 ml·kg−1 (95% CI for the difference, 7–39 ml·kg−1). TXA administration also significantly diminished (by two thirds) the perioperative exposure of patients to transfused blood (median, 1 unit vs. 3 units; P < 0.001). TXA plasma concentrations were maintained above the in vitro thresholds reported for inhibition of fibrinolysis (10 &mgr;g·ml−1) and plasmin-induced platelet activation (16 &mgr;g·ml−1) throughout the infusion. Conclusions:TXA is effective in reducing perioperative blood loss and transfusion requirement in children undergoing craniosynostosis reconstruction surgery.

Quantitative assessment of cutaneous thermal and vibration sensation and thermal pain detection thresholds in healthy children and adolescents

Quantitative sensory testing (QST) is a noninvasive, computer‐assisted method for assessing function in peripheral small and large sensory fibers. In order to use QST for clinical neurological assessment in children, it is necessary: (1) to determine whether children can reliably perform these tests and (2) to characterize normal ranges in healthy children. Values of cold sensation, warm sensation, cold pain, heat pain, and vibration sensation detection thresholds were determined in the hand and foot with the method of limits (MLI) and method of levels (MLE) in 101 healthy children aged 6–17 years using a commercially available device. Both MLI and MLE were well‐accepted by children, and there was good reproducibility between two sessions. The MLE takes longer to perform but produces lower thermal detection thresholds than the MLI. In the MLI, vibration and warm sensation showed higher thresholds in the foot than hand, whereas cold pain showed lower thresholds in the foot than hand. Based on these results, QST may be used to document and monitor the clinical course of sensory abnormalities in children with neurological disorders or neuropathic pain.

Comparison of morphine and methadone for prevention of postoperative pain in 3- to 7-year-old children*

A randomized, double-blind, prospective study was performed to determine the effects of perioperative administration of morphine or methadone on postoperative analgesic requirements and pain scores in 35 children aged 3 to 7 years undergoing major surgery. After a standardized induction of anesthesia, methadone or morphine, 0.2 mg/kg, was blindly administered, and supplemental doses were titrated to achieve comfort in the recovery room. Pain was assessed during the next 36 hours with a combination of validated behavioral and self-report measures. Patients in the methadone group required fewer supplemental opioid analgesic drugs during the next 36 hours, and reported lower pain scores. No patient had prolonged emergence from anesthesia, and no patient required naloxone or postoperative ventilatory assistance. No major adverse events occurred. We conclude that perioperative intravenous administration of methadone is an effective, inexpensive, and technologically simple means for providing prolonged analgesia for children after surgery.

Tranexamic acid diminishes intraoperative blood loss and transfusion in spinal fusions for duchenne muscular dystrophy scoliosis.

Study Design. Retrospective review of intraoperative blood loss and blood replacement. Objective. We compared intraoperative blood loss and blood replacement during spinal fusion surgery for scoliosis in Duchenne muscular dystrophy (DMD) performed with and without the synthetic antifibrinolytic agent tranexamic acid (TXA). Summary of Background Data. High levels of intraoperative blood loss are widely documented in DMD patients undergoing posterior spinal fusion for scoliosis. The effect of the antifibrinolytic agent tranexamic acid on decreasing the blood loss has not been studied in a large group of DMD patients. Methods. All 56 DMD patients underwent posterior spinal fusion with the same technique using 2 rods and multiple sublaminar wires. TXA was not used in 36 patients and was used in 20. In the respective groups, the age at surgery (14 vs. 13.9 years), the preoperative deformity (45° vs. 51°), the mean number of levels fused (14.3 vs. 14.7), and the mean surgical times (446 minutes vs. 459 minutes) were similar. TXA dose was 100 mg/kg in solution over 15 minutes before incision followed by an infusion of 10 mg/kg per hour during surgery. Standardized measurements of intraoperative blood loss were used and calculated to compare total amount of blood loss in milliliters per patient and blood loss as a percentage in relation to estimated blood volume [estimated blood loss (EBL)/estimated blood volume (EBV) × 100]. The EBV was calculated to be 70 mL/kg (body weight). Results. Mean blood loss with TXA was 1944 ± 789 mL (range, 760–4000 mL) and without TXA was 3382 ± 1795 mL (range, 600–9580 mL) (P < 0.001). Blood loss with TXA decreased by 42% compared with those not treated with TXA. Accounting for patient weight and estimated blood volume, mean % blood loss with and without TXA was 47% ± 28% versus 112% ± 67% (P < 0.001). This physiologic indicator shows that blood loss with TXA decreased by 58% compared with those patients not treated with TXA. TXA was also found to reduce blood loss after accounting for surgical time. No hypercoagulation or other complications from TXA therapy were obs-erved. The reduced blood loss in TXA-treated patients translated into decreased blood transfusions. Transfusion of homologous whole blood and packed red blood cells in the TXA group was decreased by 46% compared with the no TXA group (mean levels, 512 ± 470 mL vs. 955 ± 718 mL), and transfusion of autologous cell saver blood was decreased by 42% in the TXA group (mean levels, 419 ± 235 mL vs. 728 ± 416 mL). Conclusion. TXA significantly reduces both intraoperative blood loss and the need for homologous transfusion of whole blood and packed red blood cells in DMD patients undergoing posterior spinal fusion for scoliosis.

Blood loss in pediatric spine surgery

This article reviews the extent of blood loss in spine surgery for scoliosis corrections in the pediatric age group. An extensive literature review presents blood loss values in surgery for adolescent idiopathic scoliosis, cerebral palsy, Duchenne muscular dystrophy, spinal muscular atrophy, and myelomeningocoele. The underlying disorder plays a major role in determining the extent of blood loss. Blood loss is considerably higher in those patients with a neuromuscular scoliosis compared with adolescent idiopathic scoliosis. Within the neuromuscular group those with Duchenne muscular dystrophy demonstrate the highest mean levels of blood loss. Blood loss is also shown to be progressively greater with increasing numbers of vertebral levels incorporated into the fusion, with posterior fusions compared to anterior fusions, and in those patients having both anterior and posterior fusions.

The substance P receptor antagonist CP‐99,994 reduces acute postoperative pain

Animal studies suggest that substance P, a peptide that preferentially activates the neurokinin‐1 (NK1) receptor, is involved in pain transmission, with particular importance in pain after inflammation.