Kari Vanamo

Pharmacokinetics of Oxycodone After Intravenous, Buccal, Intramuscular and Gastric Administration in Children

ObjectiveTo evaluate the pharmacokinetics of four administration routes of oxycodone parenteral liquid (10 mg/mL), single intravenous and intramuscular injections and buccal and gastric administration, in children.Patients and participantsForty generally healthy children, aged 6–93 months, undergoing inpatient surgery.MethodsAfter induction of anaesthesia, children received a single dose of oxycodone 0.1 mg/kg intravenously (n = 9), intramuscularly (n = 10), buccally (n = 11) or via an orogastric tube into the stomach (n = 10). Regular blood samples were collected up to 12 hours, and plasma was analysed for oxycodone using gas chromatography-mass spectrometry (limit of quantification 1 µg/L).ResultsThe peak drug concentration observed was 57–110 (mean 82) µg/L after intravenous administration, 23–54 (34) µg/L after intramuscular administration, 3.9–14 (9.8) µg/L after buccal administration and 1.7–15 (9.2) µg/L after gastric administration. The time to peak concentration was 2–30 (16) minutes in the intramuscular group, 30–480 (221) minutes in the buccal group and 60–360 (193) minutes in the gastric group. The terminal elimination half-lives were closely similar in the four groups: 124–208 (163) minutes in the intravenous group, 162–227 (150) minutes in the intramuscular group, 73–234 (150) minutes in the buccal group and 80–246 (147) minutes in the gastric group. Area under the concentration-time curve (AUC) was 5037–8954 (6612) µg · min/L in the intravenous group, 3084–5524 (4473) µg · min/L in the intramuscular group, 1444-5560 (3658) µg · min/L in the buccal group and 692–3843 (2436) µg · min/L in the gastric group. The estimated bioavailability (AUC/mean intravenous AUC) of intramuscular oxycodone was 0.47–0.84 (0.68), that of buccal oxycodone 0.22–0.84 (0.55) and that of gastric oxycodone 0.10–0.58 (0.37).ConclusionThe pharmacokinetics of intravenous oxycodone in children aged 6–93 months are fairly similar to those reported in adults. Intramuscular administration provides relatively constant drug absorption, but after buccal and gastric administration the interindividual variation in the rate and extent of absorption is large.

Congenital Diaphragmatic Hernia-Does the Side of the Defect Influence the Incidence of Associated Malformations?

BACKGROUND/PURPOSE Patients with congenital diaphragmatic hernia (CDH) frequently have associated anomalies. Experiments in the nitrofen CDH model have shown differential embryonic cell death patterns in rodents suggesting unique mechanisms in the formation of right-sided (RCDH) or left-sided (LCDH) diaphragmatic hernia. These findings provide insight into the pathogenesis of CDH and may aid our understanding on the spectrum of associated anomalies commonly observed in humans. This study therefore set out to test the hypothesis that the side of the diaphragmatic defect in humans is related to the incidence and severity of coexistent organ malformations. METHODS The medical and autopsy records of 301 CDH patients presenting to two institutions over a 23-year period were examined to analyze these factors. RESULTS One hundred patients (33%) were found to have one or more associated anomalies. The incidence of multiple-RCDH (10%) versus LCDH (7.3%) and cardiac anomalies-RCDH (10%) versus LCDH (8.5%) was similar in both groups of patients. However, the hypoplastic heart syndrome was a unique feature in 5 of 22 patients (23%) with LCDH who had cardiac abnormalities. This cardiac anomaly may be related developmentally to LCDH. CONCLUSION The cellular mechanisms underlying the genesis of this spectrum of abnormalities in humans and the nitrofen CDH model warrant further study to elucidate factors governing embryonic cell fate and phenotype expression.

A diagnostic score for children with suspected appendicitis

Background/purposeAppendicectomy is an operation that is often performed without certainty of diagnosis. This study aimed to construct and to validate a prognostic score for the diagnosis of acute appendicitis in children.MethodsData for 35 symptoms and signs were prospectively recorded for 131 consecutive children with suspected appendicitis. Logistic regression analysis of the variables yielded a diagnostic score: gender (male 2 points, female 0) + intensity of abdominal pain (severe 2, mild or moderate 0) + relocation of pain (yes 4, no 0) + vomiting (yes 2, no 0) + pain in the right lower abdominal quadrant (yes 4, no 0) + fever (yes 3, no 0) + guarding (yes 4, no 0) + bowel sounds (abnormal 4, normal 0) + rebound tenderness (yes 7, no 0). The cut-off level for recommendation of appendicectomy was ≥21, and the cut-off level for non-appendicitis was ≤15. The score was prospectively validated on 109 children.ResultsIn the validation sample, based on clinical judgment, unnecessary appendicectomy was performed in ten (27%) children, and one (4%) child was misdiagnosed as not having appendicitis. By application of the score, unnecessary appendicectomies would have been reduced to four (13%), and three children (11%) with appendicitis would have been discharged.ConclusionThe use of a predictive mathematical model may facilitate the diagnosis of appendicitis to avoid unnecessary operations.

Comparison of Oxycodone Pharmacokinetics after Buccal and Sublingual Administration in Children

ObjectiveWe evaluated and compared the pharmacokinetics of two oral administration routes of oxycodone parenteral liquid (10 mg/mL) - single buccal and sublingual administration - in 30 generally healthy awake children, aged 6–91 months.MethodsTwo groups of children undergoing inpatient surgery were enrolled. In a randomised fashion, children received a single dose of oxycodone 0.2 mg/kg buccally (n = 15) or sublingually (n = 15). Regular blood samples were collected for up to 12 hours, and plasma was analysed for oxycodone, oxymorphone and noroxycodone using gas chromatography-mass spectrometry.ResultsBioavailability was similar after administration at the two instillation sites. The area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC∞) was 2400–8000 ng · min/mL (median 4200 ng · min/mL) in the buccal group and 2700-7900 ng · min/mL (median 5500 ng · min/mL) in the sublingual group. After buccal administration, maximum plasma concentration (Cmax) was 5.4–39 ng/mL (16 ng/mL) after buccal and 5.5–42 ng/mL (22 ng/mL) after sublingual administration. Twelve of the 15 children in both groups reached the oxycodone analgesic concentration of 12 ng/mL, which was sustained for 43–209 minutes (median 160 minutes) in the children with buccal oxycodone and for 32–262 minutes (median 175 minutes) in the children with sublingual oxycodone. The terminal elimination half-lives were closely similar in the two groups: 104–251 minutes (median 140 minutes) in the buccal group and 110–190 minutes (150 minutes) in the sublingual group.ConclusionThe results of this study show that in young children the absorption of oxycodone is similar after buccal and sublingual instillation.

Laparoscopic Versus Open Orchidopexy in Children with Intra-abdominal Testes

BACKGROUND/PURPOSE The management of intra-abdominal testis has been controversial but has changed significantly since the introduction of the laparoscopic technique. The aim of our study was to evaluate the success rate of laparoscopic orchidopexy (LO) compared with that of open orchidopexy (OO). MATERIALS AND METHODS In Kuopio University Hospital, 35 of 357 children with undescended testes treated between January 1992 and December 2004 had intra-abdominal testes. A retrospective review was performed to compare the outcomes of children having LO with those who had undergone OO. RESULTS Sixteen children with 19 intra-abdominal testes underwent LO and 18 children with 18 intra-abdominal testes underwent OO. Primary LO was performed in 14 children with 17 testes and staged Fowler-Stephens LO in 2 children. One LO was converted to OO. The mean (+/- standard deviation) operating time was 62 (+/- 30) minutes in the LO group and 43 (+/- 12) minutes in the OO-group (mean difference of 19 minutes, 95% confidence interval of the difference of 2 to 34 minutes; P = 0.025). There were no differences in the length of hospital stay between the two groups. Two major intra-abdominal complications occurred: 1 child in the LO-group had spermatic vessels torn, which led to a one-stage Fowler-Stephens orchidopexy, and the other child, one who had undergone a conversion from LO to OO, had a transection of the vas. One child in both groups was lost to follow-up. The overall success rate (acceptable scrotal position of the testis without testicular atrophy) was 88% in the LO group and 82% in the OO group. CONCLUSIONS Although marginally longer in duration, primary LO appears to be a feasible, safe technique for the management of the low intra-abdominal testes, whereas the staged Fowler-Stephens LO may be more safe than primary LO in cases with high intra-abdominal testes.

An autochthonous case of cystic echinococcosis in Finland, 2015.

We report a case of pulmonary cystic echinococcosis in a child from eastern Finland with no history of travelling abroad. The cyst was surgically removed and the organism molecularly identified as Echinococcus canadensis genotype G10. This parasite is maintained in eastern Finland in a sylvatic life cycle involving wolves and moose; in the present case, the infection was presumably transmitted by hunting dogs.