Yuan-Chi Lin

Acetaminophen developmental pharmacokinetics in premature neonates and infants: A pooled Population analysis

Background The aim of this study was to describe acetaminophen developmental pharmacokinetics in premature neonates through infancy to suggest age-appropriate dosing regimens. Methods A population pharmacokinetic analysis of acetaminophen time–concentration profiles in 283 children (124 aged ≤ 6 months) reported in six studies was undertaken using nonlinear mixed-effects models. Neonates and infants were given either single or multiple doses of four different formulations: oral elixir, rectal solution, or triglyceride or capsular suppository. The median postnatal age of children younger than 6 months was 1 day (range, birth to 6 months), median postconception age was 40 weeks (range, 28–64 weeks), and median weight was 3.1 kg (range, 1.2–9.0 kg). Results Population pharmacokinetic parameter estimates and their variability (percent) for a one-compartment model with first-order input, lag time, and first-order elimination were as follows: volume of distribution, 66.6 l (20%); clearance, 12.5 l/h (44%); standardized to a 70-kg person using allometric “1/4 power” models. The volume of distribution decreased exponentially with a maturation half-life of 11.5 weeks from 109.7 l/70 kg at 28 weeks after conception to 72.9 l/70 kg by 60 weeks. Clearance increased from 28 weeks after conception (0.74 l · h−1 · 70 kg−1) with a maturation half-life of 11.3 weeks to reach 10.8 l · h−1 · 70 kg−1 by 60 weeks. The absorption half-life for the oral elixir preparation was 0.21 h (120%) with a lag time of 0.42 h (70%), but absorption was further delayed (2 h) in premature neonates in the first few days of life. Absorption half-life parameters for the triglyceride base and capsule suppositories were 0.80 h (100%) and 1.4 h (57%), respectively. The absorption half-life for the rectal solution was 0.33 h. Absorption lag time was negligible by the rectal route for all three formulations. The bioavailability of the capsule suppository relative to elixir decreased with age from 0.92 (22%) at 28 weeks after conception to 0.86 at 2 yr of age, whereas the triglyceride base decreased from 0.86 (35%) at 28 weeks postconception to 0.5 at 2 yr of age. The relative bioavailability of the rectal solution was 0.66. Conclusions A mean steady state target concentration greater than 10 mg/l at trough can be achieved by an oral dose of 25 mg · kg−1 · d−1 in premature neonates at 30 weeks’ postconception, 45 mg · kg−1 · d−1 at 34 weeks’ gestation, 60 mg · kg−1 · d−1 at term, and 90 mg · kg−1 · d−1 at 6 months of age. The relative rectal bioavailability is formulation dependent and decreases with age. Similar concentrations can be achieved with maintenance rectal doses of 25 (capsule suppository) or 30 (triglyceride suppository) mg · kg−1 · d−1 in premature neonates at 30 weeks’ gestation, increasing to 90 (capsule suppository) or 120 (triglyceride suppository) mg · kg−1 · d−1 at 6 months. These regimens may cause hepatotoxicity in some individuals if used for longer than 2–3 days.

Management of esophageal strictures in children with recessive dystrophic epidermolysis bullosa.

Background Recessive dystrophic epidermolysis bullosa is a rare, genetically transmitted skin disorder characterized by blister formation and scarring in response to minor trauma. One of the most debilitating features of the disease is the development of esophageal strictures, which produces profound dysphagia, exacerbating an already highly compromised nutritional status common to these patients. Due to the extreme fragility of epithelial surfaces, the optimal therapeutic approach to esophageal strictures in this setting has not been established. Methods We have developed an approach to treatment of esophageal strictures in children with epidermolysis bullosa combining upper endoscopy using small caliber endoscopes, endotracheal intubation, and fluoroscopically assisted balloon dilatation. We report our experience using this technique in 22 children who have undergone a total of 109 dilatations. Results Upper endoscopy, endotracheal intubation, and balloon dilatation were well tolerated by even very young children with epidermolysis bullosa. Dysphagia was markedly reduced post-procedure, permitting resumption of normal diet for age, including solids, within six hours of the procedure. Post-procedure recovery has been rapid and does not require admission to the hospital. Complications have been infrequent, minor, and limited to the first year of our experience. The mean interval between dilatations for all children is 11 months. All children have gained weight, and have not required steroids or phenytoin. Conclusions Balloon dilatation is a safe and effective therapy for esophageal strictures in children with recessive dystrophic epidermolysis bullosa. Limited upper endoscopy and endotracheal intubation are well tolerated by these children. This approach should be considered as primary therapy in this clinical setting.

Plasma concentrations after rectal administration of acetaminophen in preterm neonates

Acetaminophen is frequently administered to infants and children for its antipyretic and analgesic properties. Oral administration is the route of choice in daily practice. In some circumstances this is impractical. Rectal administration of acetaminophen is an alternative route. This study measures plasma concentrations following rectal administration of acetaminophen 20 mg·kg−1 (10% Infants’ Tylenol Drops, McNeil Consumer Product Co., diluted with an equal volume of sterile water) in five preterm neonates. Serial arterial blood samples were obtained at 0, 15, 30, 60, 120, and 240 min. Pharmacokinetic parameters were (mean±sd): Cmax (maximum plasma concentration) of 8.38±3.92 μg·ml−1 and Tmax (time to reach maximum plasma concentration) of 78.0±40.2 min. Our results show that 20 mg·kg−1 of acetaminophen rectally results in low plasma levels in preterm neonates.

Acupuncture management of pain and emergence agitation in children after bilateral myringotomy and tympanostomy tube insertion

Aim:  To further investigate the effect of acupuncture in postoperative pain and emergence agitation in children undergoing bilateral myringotomy and tympanostomy tube (BMT) placement.

Paediatric selective bronchial blocker

Optimal conditions for pulmonary lobectomy requires the use of a ventilation system which allows the collapse of the ipsilateral lung. In infants and small children, a double lumen tracheal tube cannot be used because an appropriately sized tube is not widely available. We report the successful use of a tracheal tube, along which a Fogarty arterial catheter was passed and inflated in a mainstem bronchus, thus providing adequate ventilation and oxygenation as well as optimal surgical conditions for a left lower lobe lobectomy.

The impact of price labeling of muscle relaxants on cost consciousness among anesthesiologists

STUDY OBJECTIVE To determine whether placing price labels on the vial caps of muscle relaxants increases cost consciousness among anesthesiologists. DESIGN Retrospective study. SETTING University hospital departments of anesthesia and pharmacy. MEASUREMENTS AND MAIN RESULTS We placed price labels on the vial caps of all muscle relaxants for a study period of 1 year. At the beginning of the investigation, we informed the anesthesiologists of the study, discussed the prices for different muscle relaxants, and encouraged utilizing less expensive muscle relaxants whenever possible without compromising patient care. The price labels on the vial caps served as visual reminders of the various costs of muscle relaxants during daily practice. We compared the total amount spent on each muscle relaxant during the period from October 1993 to September 1994 with the period from October 1994 to September 1995. The total number of surgical cases from October 1993 to September 1994 and from October 1994 to September 1995 was unchanged and equaled 20,389 and 20,358 cases, respectively. Expenditures for pancuronium increased 104.1%. Total expenditure decreased by 12.5%, with a net savings of

Perioperative usage of acupuncture.

47,111. CONCLUSION Expenditures for the less costly pancuronium increased while expenditures for vecuronium and atracurium decreased. Price labeling of muscle relaxants in conjunction with education reduces total pharmacy expenditure on muscle relaxants.

Epidural abscess following epidural analgesia in pediatric patients

Acupuncture is a treatment modality in Traditional Chinese Medicine. It has been practiced for more than 3000 years. The Huang Di Nei Jing (The Yellow Emperor’s Internal Classic), first compiled around 100 BC, described the practice of acupuncture. The word acupuncture is derived from the Latin words acus, needle and punctura, a pricking . The acupuncture is performed by inserting special hair-thin needles into the skin at specific sites, known as acupuncture points, for desired therapeutic and preventive purposes. Acupuncture is called Jin Jiao in Chinese. It consists with the practice of acupuncture and moxibustion . Moxibustion, warming sensation of moxa (Artemisia vulgaris) over the acupuncture points, can also be used for the treatment of various illnesses. Other modalities of acupuncture practice include electro-acupuncture, cupping, laser acupuncture, acupressure, Chinese Tui-Nai massage, etc. Acupuncture as a therapeutic intervention is currently widely practiced. The U.S. National Institute of Health consensus development conference on acupuncture concludes that there are promising results supporting the efficacy of acupuncture in adult postoperative and chemotherapy-related nausea and vomiting and in postoperative dental pain. In other situations, such as addiction, stroke rehabilitation, headache, menstrual cramps, tennis elbow, fibromyalgia, myofascial pain, osteoarthritis, low back pain, carpal tunnel syndrome, and asthma, acupuncture may be useful as an adjunct treatment, as an acceptable alternative, or be included in a comprehensive management program (1). Defining and explaining the nature phenomena of acupuncture by the ancient Chinese and the theory of Traditional Chinese Medicine involve the conceptions of Yin and Yang and the Five Phases . The concept of Yin and Yang is explicit, but its connotation is philosophical. Yin and Yang are interdependent, existing in a constant state of dynamic balance. They can transform into each other, and are natural phenomena that also exist within the body. Yin is present in the qualities of rest, cold, passivity, dark, inward, decrease, and female. Yang is associated with activity, hot, activity, light, outward, increase, and male. Health requires a balance of Yin and Yang within the body. Disease is characterized by a disharmony or unbalance between Yin and Yang. The balance of Yin and Yang within the body promotes in the flow of Qi (pronounced chee ). Qi is not easily translatable or definable. It signifies power, movement, and a tendency similar to energy. Qi is a functional, active part of the body. All Qi that resides in living creatures is the result from the interaction between Qi of Heaven and the Qi of Earth. The union of the Qi of Heaven and Earth creates the Qi of human being. Qi is an energy that manifests concurrently on the physical and spiritual level. Qi flows through a complex system of meridians throughout the body, maintaining life and health. These meridians are not defined by physical structures such as blood or lymphatic vessels, but by their function. The body is viewed as a dynamic system of organs connected by the flow of Qi within the meridians. Illness results from stagnation or inadequate flow of Qi through the meridians. The flow of Qi may be restored by the insertion of several very fine needles into a combination of points from the acupuncture points that exist along the meridians. The manual twirling of these needles produces a sore, heavy, or numb sensation known as De Qi ( obtaining Qi ). Acupuncture practitioners observed that the stimulating-specific acupuncture points Correspondence to: Yuan-Chi Lin, Department of Anaesthesia, Medical Acupuncture Service, Children’s Hospital Boston, Harvard Medical School, Harvard University, Boston, MA, USA (email: yuan-chi.lin@childrens.harvard.edu). Pediatric Anesthesia 2006 16: 231–235 doi:10.1111/j.1460-9592.2005.01829.x

Outcomes after single injection caudal epidural versus continuous infusion epidural via caudal approach for postoperative analgesia in infants and children undergoing patent ductus arteriosus ligation.

Epidural abscess following epidural analgesia is an unusual event especially in pediatric patients. Two patients presented with fever and local signs of infection without neurological deficit on day 4 after the initiation of epidural analgesia. Neuro‐imaging studies revealed epidural abscess. Both pediatric patients were treated successfully with intravenous antibiotics. One of the patients’ initial MRI was normal. However, the symptoms persisted and a followed‐up scan revealed epidural abscess. The other patient presented with worsening local indurations over the epidural insertion site and positive blood culture with Hemolytic streptococcus. Our experience suggests that neuro‐imaging study should be strongly considered to evaluate pediatric patients with suspicion of epidural abscess.

Acupuncture Pain Management for Patients with Cystic Fibrosis: A Pilot Study

Adequate postoperative analgesia enhances deep breathing and minimizes respiratory complications after thoracotomy. This study compares postoperative outcomes after single injection caudal epidural vs continuous infusion epidural via caudal approach for postoperative analgesia in infants and children undergoing thoracotomy for patent ductus arteriosus (PDA) ligation. A retrospective chart review was performed for 27 children who had undergone PDA ligation. The children were divided into three groups. We compared patient demographics, surgical duration, anaesthesia duration, length of ICU stay, incidence of emesis requiring treatment, time required to establish regular oral intake, requirement for supplemental intravenous opioids during the first postoperative day, and length of hospital stay. For paediatric patients undergoing PDA ligation, postoperative analgesia with continuous infusion epidural via caudal approach produced shorter ICU stay, less occurrence of postoperative emesis, earlier oral intake, elimination of intravenous opioid supplementation, and shorter hospital stay compared with single injection caudal epidural techniques.