Greta M Palmer

I.V. acetaminophen pharmacokinetics in neonates after multiple doses

BACKGROUND Pharmacokinetics of an i.v. prodrug of acetaminophen (propacetamol) in neonates after repeat dosing are reported, with scant data for i.v. acetaminophen formulation. METHODS Neonates from an intensive care unit received 6-hourly prn i.v. acetaminophen dosed according to postmenstrual age (PMA): 28-32 weeks, 10 mg kg(-1); 32-36 weeks, 12.5 mg kg(-1); and > or =36 weeks, 15 mg kg(-1). A maximum of five blood samples for assay and liver function tests (LFTs) were collected. A one-compartment linear disposition model (zero-order input; first-order elimination) was used to describe time-concentration profiles using population modelling (NONMEM). RESULTS Fifty neonates, median (range) PMA 38.6 (32-45) weeks, mean (SD) weight 2.9 (0.7) kg, received a mean of 15 doses over a median 4 days with 189 serum acetaminophen and 231 LFT measurements. Standardized population parameter estimates for a term neonate were clearance (CL) 5.24 (CV 30.5%) litre h(-1) 70 kg(-1) and volume of distribution (V) 76 (29.6%) litre 70 kg(-1). CL increased with PMA from 4.4 litre h(-1) 70 kg(-1) at 34 weeks to 6.3 litre h(-1) 70 kg(-1) at 46 weeks. The presence of unconjugated hyperbilirubinaemia was associated with reduced CL: 150 micromol litre(-1) associated with 40% CL reduction. Acetaminophen concentrations between 10 and 23 mg litre(-1) at steady state are predicted after 15 mg kg(-1) 6-hourly for a neonate of PMA 40 weeks. Hepatic enzyme analysis of daily samples changed significantly for one patient whose alanine aminotransferase concentration tripled. CONCLUSIONS The parameter estimates are similar to those described for propacetamol. There was no evidence of hepatotoxicity. Unconjugated hyperbilirubinaemia impacts upon CL, dictating dose reduction.

Guidelines for Management of Scoliosis in Rett Syndrome Patients Based on Expert Consensus and Clinical Evidence

Study Design. Modified Delphi technique. Objective. To develop guidelines for the clinical management of scoliosis in Rett syndrome through evidence review and consensus expert panel opinion. Summary of Background Data. Rett syndrome is a rare disorder and clinical expertise is thus with small case series. Scoliosis is a frequent association and the evidence base dealing with scoliosis management in this syndrome is limited. Parents of affected girls and women have expressed needs for more information about scoliosis and Rett syndrome. Methods. An initial draft of scoliosis guidelines was created based on literature review and open-ended questions where the literature was lacking. Perspectives of four parents of Rett syndrome patients informed this initial draft. Access to an online and a Microsoft Word formatted version of the draft were then sent to an international, multidisciplinary panel of clinicians via e-mail with input sought using a 2-stage modified Delphi process to reach consensus agreement. Items included clinical monitoring and intervention before the diagnosis of scoliosis; monitoring after the diagnosis of scoliosis; imaging; therapy and conservative management; bracing; and preoperative, surgical, and postoperative considerations. Results. The first draft contained 71 statements, 65 questions. The second draft comprised 88 items with agreement to strong agreement achieved on 85, to form the final guideline document. A comprehensive, life-span approach to the management of scoliosis in Rett syndrome is recommended that takes into account factors such as physical activity, posture, nutritional and bone health needs. Surgery should be considered when the Cobb angle is approximately 40° to 50° and must be supported by specialist management of anesthesia, pain control, seizures, and early mobilization. Conclusion. Evidence- and consensus-based guidelines were successfully created and have the potential to improve care of a complex comorbidity in a rare condition and stimulate research to improve the current limited evidence base.

Recent developments in the pharmacological management of pain in children.

Purpose of review This review explores progress in developmental pharmacokinetics, pharmacogenomics and formulations of analgesic agents, and discusses potential implications for pain therapy. Recent findings Characterization of the developmental pharmacokinetics of morphine, tramadol, paracetamol and nonsteroidal anti-inflammatory drugs has improved dosing in children. Oral sugar solutions have replaced the brandy/sugar pacifier and are effective for single painful events in neonates. Intravenous paracetamol offers increased dosing accuracy, and avoids absorption and bioavailability variability. New nitric-oxide-releasing versions of paracetamol and nonsteroidal anti-inflammatory drugs offer safer alternatives to their parent drugs with enhanced potency. Ketamine has come under a cloud for its possible effects on the neonatal developing brain, but it is being used increasingly in children to supplement opioids for pain after major surgery. Hopes that morphine analgesia may improve neurological outcome in premature babies have not materialized. Reports concerning chronic pain are generally case series and controlled trials are rare and nearly nonexistent in children. Summary Unlicensed drug use in the very young will increase as familiarity increases. Pharmacogenomic studies have the potential to tailor drug therapy to the individual and decrease between-patient variability. Unfortunately, the pharmacodynamic knowledge in children of analgesic agents remains neglected and is usually extrapolated from adult data.

Acute pain management: Scientific evidence, fourth edition, 2015

This guideline summary describes the fourth edition of Acute pain management: scientific evidence, which was published by the Australian and New Zealand College of Anaesthetists (ANZCA) and its Faculty of Pain Medicine (FPMANZCA) in December 2015. The fourth edition summarises the best available evidence on acute pain management, following methods established over the preceding three editions. It provides additional information by scoring the quality of and reporting further details on randomised controlled trials and meta‐analyses. The information is condensed into key messages that provide: ➢concise statements on each topic, showing the highest level of evidence; and ➢clinical practice points based on clinical experience or expert opinion.

Use of intravenous midazolam and clonidine in cyclical vomiting syndrome: a case report

We report a case of a teenage boy with cyclical vomiting syndrome (CVS) who was referred to the anesthesia‐run postoperative pain service for symptom management. His symptoms were uncontrolled by oral pizotifen prophylaxis and acute therapy with intravenous (IV) hydration and ondansetron. A continuous low dose IV midazolam infusion was added to his treatment regimen (as is instituted for recalcitrant postoperative nausea and vomiting) with benefit, but not total symptom resolution. Recent literature review suggested links between migraine, CVS and adrenergic autonomic dysfunction. Consequently, IV clonidine was administered, in addition, with recovery. This combination was reinstituted successfully on subsequent admissions and emergency department presentations with shortened episode durations from 4–5 days to 16–48 h. It is uncertain if clonidines sympatholytic effects were significantly beneficial or if associated sedation or natural resolution were contributors. Many agents have been used in CVS therapy but no trials have been done. Neither midazolam nor clonidine has been reported previously as used in the treatment of CVS. The apparent success of this combination raises possibilities both for future trials and research into the pathogenesis of CVS.

A pilot study of inhaled methoxyflurane for procedural analgesia in children

Background:  Methoxyflurane (MF), a potent volatile anesthetic, can be used as an analgesic in subanesthetic concentrations. In Australia, MF is extensively used in children and adults as an analgesic in the prehospital setting via a hand‐held inhaler device. We conducted a pilot study to explore its use as a patient controlled analgesic for painful procedures in children in the emergency department (ED).

Neuropathic pain and foot drop related to nerve injury after short duration surgery and caudal analgesia.

Caudal anesthesia is the most common type of regional anesthetic technique performed in children. The incidence of neurologic adverse events is extremely rare. A postoperative complication of a mild but permanent neurologic deficit after administration of a caudal anesthetic in a previously well 9-year-old boy who required emergency scrotal exploration for a testicular torsion is reported. The caudal injection provided good postoperative analgesia, which probably resulted in the patient remaining in the same position overnight. This may have contributed to the development of the neurologic deficit, probably owing to a compressive neuropathy. We suggest that, as anesthesiologists obtaining informed consent for anesthetic interventions, we now need to inform guardians/carers of pediatric patients who are to receive caudal analgesia of the extremely small material risk of neurologic damage after caudal anesthesia. Additionally, the anesthetic community may need to consider revising postoperative care instructions to prevent the future occurrence of this rare outcome, particularly if using additives that prolong analgesic block duration.

Is there a role for intravenous acetaminophen in pediatric emergency departments

Background: As a nonopioid parenteral analgesic intravenous (IV) acetaminophen is potentially attractive for emergency department (ED) use. However, there is little experience with its use in the pediatric ED setting. We introduced the agent into a pediatric ED with a preliminary restrictive prescribing regimen and describe its use. Methods: This is a retrospective record review of all patients who had received IV acetaminophen over 12 months. Prescribing indications were for analgesia only (not for fever management) in patients at risk of opioid-related adverse events. We assessed the demographics, dosing, presenting complaints, discharge diagnoses, and indications for IV acetaminophen use. Results: Thirty-one patients received IV acetaminophen (mean age, 10 years). All patients were at least moderately sick according to their triage assessment. The median dose was 15 mg/kg with a median of 1 dose administered. Presenting complaints were mainly trauma, abdominal complaints, and sepsis/fever/neutropenia. Thirty-nine percent of patients had severe underlying conditions. Two patients died: 1 patient had a chronic neurological condition, and the other was undergoing palliative treatment for cancer. Physicians complied with prescribing indications for half the patients: 53% were at risk of opioid-related adverse events. Physicians prescribed outside the initial indications as part of multimodal analgesia (13%), for complex patients with fever and pain (7%), and for fever only in patients unable to tolerate enteral administration (27%). Conclusions: In the setting of an initial restrictive prescribing regimen, IV acetaminophen was used in a small number of pediatric ED patients. In addition to use in patients at risk of opioid adverse events, the medication was also used in complex patients who were unable to tolerate an enteral formulation. Emergency department prescribing guidelines have been modified accordingly.

Scope for improvement: hospital wide sedation practice at a children’s hospital

Procedural sedation by non-anaesthesia staff is frequently required in children, yet even “safe” agents can be associated with serious adverse events.1 Professional societies and professional bodies have published sedation guidelines in a number of countries.2 However, no data exist about the characteristics of sedation practice from a hospital wide perspective. We set out to determine the spectrum and quality of procedural sedation performed by non-anaesthesia staff at a tertiary paediatric hospital. All episodes of procedural sedation by non-anaesthesia staff outside intensive care units were prospectively tracked over three weeks in 2004 …

The addition of tramadol to the standard of IV acetaminophen and morphine infusion for postoperative analgesia in neonates offers no clinical benefit: a randomized placebo‐controlled trial

Tramadol is used following neonatal cardiac and general surgery. However, its ability to opioid‐spare or facilitate earlier extubation in postoperative neonates is unquantified.