Alpha-1-acid glycoprotein and its potential impact on local anesthetic dose in neonates.

BACKGROUND: Alpha-1-acid glycoprotein is an acute-phase protein with a high affinity for amide local anesthetics. Compared to adults, neonates have lower concentrations of this glycoprotein in plasma, and are therefore at higher risk of developing local anesthetic toxicity. Alpha-1-acid glycoprotein concentrations rise in adults after surgery as a response to stress as well as in inflammatory conditions. Previous studies have shown that concentrations of alpha-1-acid-glycoprotein in neonates vary postpartum, influenced by gestational age and mode of delivery. AIM: This study aims to determine the concentrations of alpha-1-acid glycoprotein pre- and postoperatively in neonates undergoing major surgery. This information is important for determining safe and effective dosage of local anesthetic in this vulnerable group of patients. METHODS: In this prospective observational study, 25 neonates (median 3 days of age) undergoing major surgery were included. Blood sampling was performed preoperatively and at four occasions postoperatively. Alpha-1-acid-glycoprotein plasma concentrations were analyzed using an immunoturbidimetric assay. Mann-Whitney U test, Kruskal-Wallis and Spearman ranking correlation test were used for the statistical analysis. RESULTS: Higher plasma concentrations of alpha-1-acid-glycoprotein were found 48 h postoperatively compared to preoperatively [median (inter-quartile range) 0.815 g L-1 (0.663-0.983 g L-1 ) vs. 0.300 g L-1 (0.205-0.480 g L-1 p < 0.001)], respectively. It was not possible to detect any influence of sex, postnatal age, gestational age, or delivery mode on alpha-1-acid-glycoprotein concentrations in our data. CONCLUSIONS: Alpha-1-acid-glycoprotein concentrations increase in neonates as a response to surgery regardless of gestational age, sex, or mode of delivery.

Improved home management of oral pediatric anticancer drugs as a result of an intervention comprising practical training, written instructions and movie clips: A pilot study.

BACKGROUND: Long term treatment of pediatric patients with oral anticancer drugs (OADs) requires the parents/caregivers to prepare the drug at home. The handling procedures in the home setting are, however, not regulated by Swedish law and the parents are often left without guidance on how to handle OADs in a safe way. AIM: The aim of this study was to increase understanding of how OADs are handled by parents/caregivers in the home setting before and after an intervention. METHODS: Parents of pediatric cancer patients were observed and videotaped during their handling of OADs in the home setting before and after the intervention. During the intervention, the parents were provided with written instructions, movie clips and practical training on handling the OADs. Four checklists were used to compare and score the four handling procedures (measuring an oral suspension, cutting tablets, dissolving tablets, and opening capsules) for each parent before and after the intervention. RESULTS: The intervention significantly improved the OAD handling procedures among the studied parents. The median score for correct handling was 19% (IQR: 3.6 to 30%) before the intervention and 89.5% (IQR: 71.5 to 94.5%) after the intervention (p < 0.0001). CONCLUSIONS: An intervention comprising practical training and information presented in different forms improved the handling of OADs at home by parents. There is an urgent need to implement this method in all oncology centers in Sweden, educate HCPs to standardize the presentation of information. There is also a great need to provide parents with age-appropriate oral drug formulations from the local hospital pharmacies in Sweden.

Parents' experiences of handling oral anticancer drugs at home: 'It all falls on me '.

AIM: The aim of this study was to describe the experiences of parents handling oral anticancer drugs in a home setting. METHODS: Parents of children with cancer were recruited from a paediatric oncology ward in Sweden to participate in an interview. The interviews were transcribed verbatim and subjected to qualitative content analysis. RESULTS: We found the following categories and subcategories: parents' views on the provided information-lack of, too little or contradictory information, and parents' preferences for information delivery; safety over time; correct drug dose; and drug administration. As time passed, most parents adapted to their child's illness, felt safer and found it easier to take in and process any given information. Parents preferred information in different formats (written, movie clips and orally) and in their mother tongue. Many parents were aware of the importance of giving an accurate dose to their child and described the process of drug administration as overwhelming. CONCLUSION: Parents need to be provided with accurate, timely, nonconflicting and repeated information-in different forms and in their mother tongue-on how to handle oral anticancer drugs at home.

Risks for death after admission to pediatric intensive care (PICU)-A comparison with the general population.

OBJECTIVE/AIM: The aim of the study was to quantify excess mortality in children after admission to a Pediatric Intensive Care Unit (PICU), compared to the age and sex matched general Swedish population. DESIGN: Single-center, retrospective cohort study. SETTING: Registry study of hospital registers, a national population register and Statistics Sweden. PATIENTS: Children admitted to a tertiary PICU in Sweden in 2008-2016. INTERVENTIONS: None. MAIN RESULTS: In total, 6,487 admissions (4,682 patients) were included in the study. During the study period 444 patients died. Median follow-up time for the entire PICU cohort was 7.2 years (IQR 5.0-9.9 years). Patients were divided into four different age groups (0-28 d, > 28 d -1 yr, > 1-4 yr, and > 4 yr) and four different risk stratification groups [Predicted Death Rate (PDR) intervals: 0-10%, > 10-25%, > 25-50%, and > 50%] at admission. Readmission was seen in 929 (19.8%) patients. The Standardized Mortality Ratios (SMRs) were calculated using the matched Swedish population as a reference group. The SMR for the entire study group was 49.8 (95% CI: 44.8-55.4). For patients with repeated PICU admissions SMR was 108.0 (95% CI: 91.9-126.9), and after four years 33.9 (95% CI: 23.9-48.0). Patients with a single admission had a SMR of 35.2 (95% CI: 30.5-40.6), and after four years 11.0 (95% CI: 7.0-17.6). The highest SMRs were seen in readmitted children with oncology/hematology (SMR = 358) and neurologic (SMR = 192) diagnosis. Children aged >1-4 years showed the highest SMR (325). In PDR group 0-10% children with repeated PICU admissions (n = 798), had a SMR of 100. CONCLUSION: Compared to the matched Swedish population, SMRs were greatly elevated up to four years after PICU admission, declining from over 100 to 33 for patients with repeated PICU admissions, and from 35 to 11 for patients with a single PICU admission.

Rapid systemic uptake of naloxone after intranasal administration in children.

BACKGROUND: Naloxone has a high affinity for the µ-opioid receptor and acts as a competitive antagonist, thus reversing the effects of opioids. Naloxone is often administrated intravenously, but there is a growing interest in the intranasal route in treating patients with opioid overdose, and in reversing effects after therapeutic use of opioids. As administration is painless and no intravenous access is needed, the intranasal route is especially useful in children. AIM: The aim of this study was to investigate the uptake of naloxone 0.4 mg/ml during the first 20 min after administration as a nasal spray in a pediatric population, with special focus on the time to achieve maximum plasma concentration. METHODS: Twenty children, 6 months-10 years, were included in the study. The naloxone dose administered was 20 µg/kg, maximum 0.4 mg, divided into repeated doses of 0.1 ml in each nostril. Venous blood samples were collected at 5, 10, and 20 min after the end of administration. RESULTS: All patients had quantifiable concentrations of naloxone in venous blood at 5 min, and within 20 min, peak concentration had been reached in more than half of the children. At 20 min after intranasal administration, the plasma naloxone concentrations were within the range of 2-6 nanogram/ml. CONCLUSION: This study confirms the clinical experience that the rapid effect of naloxone after intranasal administration in children was reflected in rapid systemic uptake to achieve higher peak plasma concentrations than previously reported in adults.

Deficits in the IgG+ memory B-cell recovery after anthracycline treatment is confined to the spleen of rhesus macaques.

OBJECTIVES: Loss of vaccine-induced antibodies (Abs) after chemotherapy against paediatric acute lymphoblastic leukaemia (ALL) is common and often necessitates re-immunisation after cessation of treatment. Even so, some ALL survivors fail to mount or to maintain protective Abs. Germinal centres (GCs) are clusters of proliferating B cells in follicles of secondary lymphoid tissues (SLTs) formed during adaptive immune responses and the origins of long-lived memory B and plasma cells that are the source of Abs. Furthermore, productive GC reactions depend on T follicular helper (TFH) cells. To understand why chemotherapy induces deficits in Ab responses, we examined how SLTs were affected by chemotherapy. METHODS: Rhesus macaques were infused with either three cycles of the anthracycline doxorubicin or saline, followed by immunisation with a de novo and booster antigen. Spleen and lymph nodes were removed, and memory B, bulk T and TFH cells were examined. RESULTS: Despite adequate GC morphology, a diminished memory and IgG+ B-cell population along with diminished total and booster vaccine-specific IgG-producing memory B cells were noted in the spleens of macaques with past doxorubicin exposure compared to the saline-treated controls (P < 0.05). Intact bulk T and TFH cells were found in the SLTs of treated macaques, which displayed higher CD40L upregulation capacity by their splenic CXCR5+ helper T cells (P < 0.01). In contrast to the spleen, the immune cell populations studied were comparable between the lymph nodes of both saline- and doxorubicin-treated macaques. CONCLUSION: Our findings suggest that the splenic memory B-cell subset, compared to its lymph node counterpart, is more severely altered by anthracycline treatment.

Does extracorporeal membrane oxygenation attenuate hypoxic pulmonary vasoconstriction in a porcine model of global alveolar hypoxia?

BACKGROUND: During severe respiratory failure, hypoxic pulmonary vasoconstriction (HPV) is partly suppressed, but may still play a role in increasing pulmonary vascular resistance (PVR). Experimental studies suggest that the degree of HPV during severe respiratory failure is dependent on pulmonary oxygen tension (PvO2 ). Therefore, it has been suggested that increasing PvO2 by veno-venous extracorporeal membrane oxygenation (V-V ECMO) would adequately reduce PVR in V-V ECMO patients. OBJECTIVE: Whether increased PvO2 by V-V ECMO decreases PVR in global alveolar hypoxia. METHODS: Nine landrace pigs were ventilated with a mixture of oxygen and nitrogen. After 15 minutes of stable ventilation and hemodynamics, the animals were cannulated for V-V ECMO. Starting with alveolar normoxia, the fraction of inspiratory oxygen (FI O2 ) was stepwise reduced to establish different degrees of alveolar hypoxia. PvO2 was increased by V-V ECMO. RESULTS: V-V ECMO decreased PVR (from 5.5 [4.5-7.1] to 3.4 [2.6-3.9] mm Hg L-1  min, P = .006) (median (interquartile range),) during ventilation with FI O2 of 0.15. At lower FI O2 , PVR increased; at FI O2 0.10 to 4.9 [4.2-7.0], P = .036, at FI O2 0.05 to 6.0 [4.3-8.6], P = .002, and at FI O2 0 to 5.4 [3.5 - 7.0] mm Hg L-1  min, P = .05. CONCLUSIONS: The effect of increased PvO2 by V-V ECMO on PVR depended highly on the degree of alveolar hypoxia. Our results partly explain why V-V ECMO does not always reduce right ventricular afterload at severe alveolar hypoxia.

Unnecessary harm is avoided by reliable paediatric index of mortality2 scores without arterial gas sampling.

AIM: To investigate whether unnecessary harm could be avoided in children admitted to paediatric intensive care (PICU), we analysed the impact of arterial blood gas on the paediatric index of mortality score2 (PIM2) and the derived predicted death rate (PDR). METHODS: From January 1, 2008 to December 31, 2010, 1793 consecutive admissions, newborn infants to 16 years of age (median 0.71 years) from a single, tertiary PICU in Gothenburg Sweden, were collected. Admission information on arterial oxygen tension (PaO2 ) and fraction of inspired oxygen (FiO2 ) was extracted from 990 admissions. RESULTS: There was close agreement between PIM2 score and PDR regardless of whether the PaO2 /FiO2 ratio was omitted or not. In the subgroup of admissions with a respiratory admission diagnosis, the inclusion of the PaO2 /FiO2 ratio increased the accuracy of the PIM2 score as well as the PDR. The standard mortality ratio was slightly but not significantly overestimated by excluding the PaO2 /FiO2 ratio. CONCLUSION: To avoid unnecessary harm to children admitted to PICU, an arterial blood gas analysis should only be performed if clinically indicated or if the child has a respiratory admission diagnosis. Estimation of the PIM2 score and PDR will not be less accurate by this approach.

Fas-ligand and interleukin-6 in the cerebrospinal fluid are early predictors of hypoxic-ischemic encephalopathy and long-term outcomes after birth asphyxia in term infants.

BACKGROUND: Cerebral ischemia generates neuroinflammation that can induce neural cell death. This cohort study assessed whether Fas-ligand (FasL) and interleukin (IL)-6 levels in the cerebrospinal fluid (CSF) after hypoxic-ischemic encephalopathy (HIE) can serve as biomarkers of hypoxic brain injury in neonates. METHODS: Term infants (> 37-week gestational age) who were admitted to the neonatal intensive care unit of Karolinska University Hospital in years 2002 to 2004 with perinatal asphyxia were enrolled prospectively. Control infants without brain pathology underwent lumbar puncture for suspected infection. FasL and IL-6 levels were measured in the CSF, by enzyme-linked immunosorbent assays. All patients underwent neurological assessment at 18 months. HIE was classified as mild, moderate, or severe (HIE I-III). Adverse neurological outcome at 18 months was defined as a mental developmental index < 85, deafness, blindness, cerebral palsy, or seizure disorder. RESULTS: Of the 44 HIE patients, 14, 16, and 14 had HIE-I, HIE-II, and HIE-III, respectively. HIE-II and HIE-III patients had higher FasL and IL-6 levels than HIE-I patients and the 20 controls (all p < 0.0001). Patients with adverse outcomes had higher FasL and IL-6 levels than patients with normal outcomes and controls (both p < 0.0001). On receiver-operator curve analyses, FasL and IL-6 (alone and together) were highly predictive of HIE grade and outcome (areas under the curve range 0.86-0.94) and showed high sensitivity (66.7-100%). These biomarkers performed better than cord blood pH (areas under the curve: HIE grade = 0.80, adverse outcomes = 0.86). CONCLUSION: CSF biomarkers FasL and IL-6 predicted severity of encephalopathy and long-term outcomes in post-asphyxiated infants better than a standard biomarker.

Interactive web-based format vs conventional brochure material for information transfer to children and parents: a randomized controlled trial regarding preoperative information.

BACKGROUND: Information transfer to patients is an integral part of modern medicine. Internet-based alternatives represent a new and attractive way for information transfer. METHODS: The study used a prospective observer-blinded design. Children (3-12 years) and parents were instructed to get further preoperative information either through an interactive web-based platform, the Anaesthesia-Web, or conventional brochure material until day of outpatient surgery. On the day of surgery, children and parents were separately asked six different questions. The primary end-point was to compare the total question score in children between the two information options (maximum score = 36). Secondary aims were the total question score for parents and the influence of age, sex, and time between the preoperative visit and day of surgery. RESULTS: A total of 125 children were recruited, of which 103 were included in the final analysis (the Anaesthesia-Web group, n = 49; the brochure material group, n = 54). At the predetermined interim analysis, the total question score in children was found to be substantially higher in the Anaesthesia-Web group than in the brochure material group (median score: 27; IQR: 16.5-33 and median score: 19.5; IQR: 11.25-27.75, respectively, P = 0.0076). The median difference in score was 6; 95% CI: 0-9. The total question score in parents was also higher in the Anaesthesia-Web group than in the brochure material group. Increasing child age was associated with a higher total question score in both groups. Sex did not influence the total question score in the Anaesthesia-Web group, whereas girls scored better than boys in the brochure material group. CONCLUSIONS: Children in the age range 3-12 years of age as well as their parents do better attain preoperative information from an interactive web-based platform compared to conventional brochure material.

Cervical necrotizing fasciitis: descriptive, retrospective analysis of 59 cases treated at a single center.

To provide retrospective, descriptive information on patients with cervical necrotizing fasciitis treated at a single center during the years 1998-2014, and to evaluate the outcome of a newly introduced treatment strategy. Retrospective analysis of clinical data obtained from medical records. Mortality, pre-morbidity, severity of illness, primary site of infection, type of bacteria, time parameters. The observed 3-month mortality was 6/59 (10 %). The most common initial foci of the infection were pharyngeal, dental or hypopharyngeal. The most common pathogen was Streptococcus milleri bacteria within the Streptococcus anginosus group (66 % of the cases). Using a combined treatment with early surgical debridement combined with hyperbaric oxygen treatment, it is possible to reduce the mortality rate among patients suffering from cervical necrotizing fasciitis, compared to the expected mortality rate and to previous historical reports. Data indicated that early onset of hyperbaric oxygen treatment may have a positive impact on survival rate, but no identifiable factor was found to prognosticate outcome.

A novel oral insulin-like growth factor-1 receptor pathway modulator and its implications for patients with non-small cell lung carcinoma: A phase I clinical trial.

BACKGROUND: A phase Ia/b dose-escalation study was performed to characterize the safety, efficacy and pharmacokinetic properties of the oral small molecule insulin-like growth factor-1-receptor pathway modulator AXL1717 in patients with advanced solid tumors. MATERIAL AND METHODS: This was a prospective, single-armed, open label, dose-finding phase Ia/b study with the aim of single day dosing (phase Ia) to define the starting dose for multi-day dosing (phase Ib), and phase Ib to define and confirm recommended phase II dose (RP2D) and if possible maximum tolerated dose (MTD) for repeated dosing. RESULTS AND CONCLUSION: Phase Ia enrolled 16 patients and dose escalations up to 2900 mg BID were successfully performed without any dose limiting toxicity (DLT). A total of 39 patients were treated in phase Ib. AXL1717 was well tolerated with neutropenia as the only dose-related, reversible, DLT. RP2D dose was found to be 390 mg BID for four weeks. Some patients, mainly with NSCLC, demonstrated signs of clinical benefit, including four partial tumor responses (one according to RECIST and three according to PET). The 15 patients with NSCLC with treatment duration longer than two weeks with single agent AXL1717 in third or fourth line of therapy showed a median progression-free survival of 31 weeks and overall survival of 60 weeks. Down-regulation of IGF-1R on granulocytes and increases of free serum levels of IGF-1 were seen in patients treated with AXL1717. AXL1717 had an acceptable safety profile and demonstrated promising efficacy in this heavily pretreated patient cohort, especially in patients with NSCLC. RP2D was concluded to be 390 mg BID for four weeks. Trial number is NCT01062620.

Pharmacokinetics and Toxicity of Sodium Selenite in the Treatment of Patients with Carcinoma in a Phase I Clinical Trial: The SECAR Study.

BACKGROUND: Sodium selenite at high dose exerts antitumor effects and increases efficacy of cytostatic drugs in multiple preclinical malignancy models. We assessed the safety and efficacy of intravenous administered sodium selenite in cancer patients' refractory to cytostatic drugs in a phase I trial. Patients received first line of chemotherapy following selenite treatment to investigate altered sensitivity to these drugs and preliminary assessment of any clinical benefits. MATERIALS AND METHODS: Thirty-four patients with different therapy resistant tumors received iv sodium selenite daily for consecutive five days either for two weeks or four weeks. Each cohort consisted of at least three patients who received the same daily dose of selenite throughout the whole treatment. If 0/3 patients had dose-limiting toxicities (DLTs), the study proceeded to the next dose-level. If 2/3 had DLT, the dose was considered too high and if 1/3 had DLT, three more patients were included. Dose-escalation continued until the maximum tolerated dose (MTD) was reached. MTD was defined as the highest dose-level on which 0/3 or 1/6 patients experienced DLT. The primary endpoint was safety, dose-limiting toxic effects and the MTD of sodium selenite. The secondary endpoint was primary response evaluation. RESULTS AND CONCLUSION: MTD was defined as 10.2 mg/m(2), with a calculated median plasma half-life of 18.25 h. The maximum plasma concentration of selenium from a single dose of selenite increased in a nonlinear pattern. The most common adverse events were fatigue, nausea, and cramps in fingers and legs. DLTs were acute, of short duration and reversible. Biomarkers for organ functions indicated no major systemic toxicity. In conclusion, sodium selenite is safe and tolerable when administered up to 10.2 mg/m(2) under current protocol. Further development of the study is underway to determine if prolonged infusions might be a more effective treatment strategy.

Protective role of humanin on bortezomib-induced bone growth impairment in anticancer treatment.

BACKGROUND: Bortezomib is a proteasome inhibitor currently studied in clinical trials of childhood cancers. So far, no side effects on bone growth have been reported in treated children. However, bortezomib was recently found to induce apoptosis in growth plate chondrocytes and impair linear bone growth in treated mice. We hypothesize that [Gly(14)]-humanin (HNG), a 24-amino acid synthetic antiapoptotic peptide, can prevent bortezomib-induced bone growth impairment. METHODS: Mice with human neuroblastoma or medulloblastoma tumor xenografts (9-13 animals/group) received one 2-week cycle (2 injections/week) of bortezomib (0.8 mg/kg or 1.0mg/kg), or HNG (1 µg/mouse), or the combination of HNG/bortezomib, or vehicle. Cultures of human growth plate cartilage, chondrogenic- and cancer cell lines, and immunohistochemistry for detection of proapoptotic proteins were also used. Statistical significance was evaluated by two-sided Mann-Whitney U test or by parametric or nonparametric analysis of variance. RESULTS: Bortezomib efficiently blocked the proteasome and induced pronounced impairment of linear bone growth from day 0 to day 13 (0.09 mm/day, 95% confidence interval [CI] = 0.07 to 0.11 mm/day; vs 0.19 mm/day, 95% CI = 0.15 to 0.23 mm/day in vehicle; P < .001), an effect significantly prevented by the addition of HNG (0.15 mm growth/day, 95% CI = 0.14 to 0.16 mm/day; P < .001 vs bortezomib only; P = 0.03 vs vehicle). Bortezomib was highly toxic when added to cultures of human growth plate cartilage, with markedly increased apoptosis compared with control (P < .001). However, when combining with HNG, bortezomib-induced apoptosis was entirely prevented, as was Bax and PARP activation. Bortezomib delayed tumor growth, and HNG did not interfere with the anticancer effect when studied in human tumor xenografts or cell lines. CONCLUSIONS: HNG prevents bortezomib-induced bone growth impairment without interfering with bortezomib's desired anticancer effects.

Jejunostomy enteral feeding in children: outcome and safety.

BACKGROUND: The aim of this study was to report on the clinical outcome and safety of jejunostomy tube feeding used in our clinical setting for more than 14 years. MATERIAL AND METHODS: A retrospective study of all children who underwent a surgical catheter jejunostomy placement between July 1996 and March 2010 was conducted. Data were collected regarding the outcome and complications. RESULTS: Thirty-three children (14 girls) were included. The median age at the time of primary surgery was 1.43 years (range, 0.15-17.7 years), and the median time of follow-up was 2.34 years (range, 0.27-12.6 years). Seventeen children were severely neurologically impaired (NI). Surgical insertion of a jejunostomy tube was performed due to 1 or more of the following indications: gastroesophageal reflux disease (GERD), failure to thrive, recurrent pneumonia, esophageal disease, or oral feeding difficulties. The effect of the indications showed a reduction in GERD and pneumonia. Feeding difficulties also decreased. Weaning was possible in 12 of 16 children without NI but in only 2 of 17 with NI. Major complications requiring surgical reoperation affected 8 children. No mortality was related to the jejunostomy feeding catheter. CONCLUSION: In selected cases, surgically placed jejunostomy tubes for feeding in children is an effective and safe method to overcome GERD, feeding difficulties, or recurrent pneumonia without major surgery.

Impact of prior traumatic life events on parental early stage reactions following a child's cancer.

BACKGROUND: In pediatric oncology, effective clinic-based management of acute and long-term distress in families calls for investigation of determinants of parents' psychological response to the child's cancer. We examined the relationship between parents' prior exposure to traumatic life events (TLE) and the occurrence of posttraumatic stress symptoms (PTSS) following their child's cancer diagnosis. Factors mediating the TLE-PTSS relationship were analyzed. METHODOLOGY: The study comprised 169 parents (97 mothers, 72 fathers) of 103 cancer diagnosed children (median age: 5,9 years; range 0.1-19.7 years). Thirty five parents were of immigrant origin (20.7%). Prior TLE were collated using a standardized questionnaire, PTSS was assessed using the Impact of Events-Revised (IES-R) questionnaire covering intrusion, avoidance and hyperarousal symptoms. The predictive significance of prior TLE on PTSS was tested in adjusted regression models. RESULTS: Mothers demonstrated more severe PTSS across all symptom dimensions. TLE were associated with significantly increased hyperarousal symptoms. Parents' gender, age and immigrant status did not significantly influence the TLE-PTSS relationship. CONCLUSIONS: Prior traumatic life-events aggravate posttraumatic hyperarousal symptoms. In clinic-based psychological care of parents of high-risk pediatric patients, attention needs to be paid to life history, and to heightened vulnerability to PTSS associated with female gender.

Onset time for pharmacologic premedication with clonidine as a nasal aerosol: a double-blind, placebo-controlled, randomized trial.

OBJECTIVES/AIM: To investigate whether nasal aerosol clonidine can reduce the onset time of preoperative sedation. BACKGROUND: Premedication is common in the pediatric population, but the optimal agent and administration route is still a matter of debate. Clonidine has many beneficial effects in the perioperative period. Clonidine nasal drops produce a similar sedative effect as after oral administration but do not reduce the onset time. Nasal aerosol administration of drugs is generally more effective than drops and an option to decrease the onset time of clonidine. METHODS: Pediatric ASA status 1 and 2 patients were randomized to receive placebo (P), clonidine 3-4 µg kg(-1) (C4), or clonidine 7-8 µg kg(-1) (C7) as a nasal aerosol. Acceptance of administration, pre- and postoperative sedation, and adverse events were assessed. RESULTS: A total of 60 patients were enrolled with a median age of 3.5 years (range 0.7-6.9) and median weight of 14.8 kg (range 10-25). In the C7 group, 55% of the children were found adequately sedated at 30 min as compared to 32% in the C4 group (P = 0.1202). At 45 min, adequate sedation was seen in 65% of the patients in both C4 and C7 groups, which were both found to be significantly higher compared with the placebo control group (14%) (P-values = 0.0027 and 0.0013, respectively). The postoperative sedation profile did not differ between the three study groups. CONCLUSIONS: Clonidine administered as nasal aerosol (3-8 µg kg(-1)) was not found to achieve adequate preoperative sedation within 30 min of administration. Despite its sedative properties, no prolongation of postoperative sedation was noted compared with placebo.

Estimation of body surface area in various childhood ages--validation of the Mosteller formula.

AIM: The aim of the present study was to validate the Mosteller formula for the estimation of body surface area (BSA) in various childhood ages. Many physiological processes including drug metabolism correlate with values for BSA. In addition, dosing of many drugs, especially drugs with low therapeutic index, for example, anti-neoplastics, are based on estimated values of BSA. METHODS: Published data from measured BSA in 268 children and infants (median age: 8 month; range: 0-18 years) were compared with BSA values estimated by the Mosteller formula. Correlation between estimated and measured BSA values was performed by the Spearman rank correlation. Bias and precision were evaluated as outlined by Sheiner and Beal. Measured and estimated BSA values were compared by the Eksborg's plot. RESULTS: Measured values of BSA and BSA values estimated by the Mosteller formula were closely correlated (r(s) = 0.973; p < 0.0001). The formula of Mosteller had with a precision of 9.38% and underestimated BSA by 4.06%. The quotients Estimated/Measured BSA were within the range 0.9-1.1 in 71.3% of the observations, but deviation up to 35% occurred. CONCLUSION: The Mosteller formula underestimates BSA in the paediatric population and must be used with precautions because of low precision, most pronounced in neonates and infants.