Inappropriate early hypotension in adolescents: a form of chronic orthostatic intolerance with defective dependent vasoconstriction.

Instantaneous orthostatic hypotension (INOH) has been reported in children and adolescents as a new entity of orthostatic intolerance in children who underwent rapid standing as an orthostatic stress test. Children with INOH were discovered among patients presenting with symptoms of chronic orthostatic intolerance, which is often related to orthostatic tachycardia. We used head-up tilt table testing at 70 degrees to investigate children presenting with symptoms of chronic orthostatic intolerance. We compared 24 patients aged 12-17 y, with chronic orthostatic intolerance and symptoms for >or=3 mo, with 13 healthy normal control patients. We recorded continuous heart rate, blood pressure, and respiratory rate and used venous occlusion strain gauge plethysmography to measure calf and forearm blood flow while supine and calf blood flow during head-up tilt. Patients with chronic orthostatic intolerance fulfilled criteria for the postural orthostatic tachycardia syndrome. Postural orthostatic tachycardia syndrome patients were divided into two groups by the occurrence of INOH. Supine forearm and calf arterial resistance was decreased in patients with INOH (n = 8) compared with postural orthostatic tachycardia syndrome patients without INOH (n = 16) and compared with control (n = 13). Resting calf venous pressure was elevated, suggesting excess venous filling because of vasodilation. During early head-up tilt, calf blood flow increased markedly in INOH, less in No-INOH, postural orthostatic tachycardia syndrome patients and least in control patients. Flow was temporally related to calf swelling and negatively correlated to hypotension. The data suggest that INOH occurs in patients with chronic orthostatic intolerance and orthostatic tachycardia and is related to rapid caudal blood flow when upright because of a vasoconstrictor defect.     

Episodic hypertension in postural orthostatic tachycardia syndrome

We report the case of a 17-year-old woman who presented to the emergency department on several occasions due to palpitations, tachycardia, syncope, short spells of dizziness and light-headedness with complete spontaneous recovery, and hypertension. The patient had been evaluated by several specialists, and multiple complementary examinations had revealed no abnormalities that could explain the symptoms. Due to suspicion of orthostatic intolerance or postural orthostatic tachycardia syndrome with hypertension, the patient underwent a 60-degree tilt table test, which confirmed the diagnosis. The patient was successfully treated with bisoprolol. The physiopathological mechanisms, diagnosis, and treatment of this syndrome are reviewed.     

体位性心动过速综合征109例临床特征分析

探讨儿童体位性心动过速综合征（POTS）的临床特点。方法　2008年5月至2009年10月于北京大学第一医院儿科门诊就诊,经直立试验或直立倾斜试验确诊POTS的患儿109例（POTS组）,平均年龄（11.79±2.55）岁;20名健康儿童为对照组,平均年龄（11.55±3.65）岁。对每例POTS患儿详细询问病史并进行体格检查,对比分析两组儿童在生活习惯、家族史及体质特征方面特点,总结POTS组患儿发病的临床特征。结果　与对照组相比,POTS组患儿在性别比例、年龄、身高、体重、平卧心率、平均动脉压方面差异无统计学意义。POTS患儿主要症状以晕厥多见（52.3%）,42.2％症状发作频繁（就诊时 > 10次）,主要症状发生季节以夏秋季多见（42.1%）, 发作持续时间多在1 min以内（29%）。83.5%患儿发作前有诱因,发作诱因以持久站立为多见（50.5%）,发作前多伴有先兆症状（78.0%）,其中以头晕、黑矇、大汗、面色苍白最为常见。18例（16.5%）患儿有伴随症状,32例（29.4%）发作后仍有不适,以乏力最常见（24例）。90例（82.6%）患儿无既往疾病史,30例（27.6%）有直立不耐受家族史,46例（42.2%）有晕车经历。POTS组清淡饮食者居多（41.3%）,水摄入较少（63.3%）。结论　儿童POTS多发生于学龄期及青春期,晕厥发生率较高,发作季节以夏秋季多见,持久站立、体位改变、精神紧张以及感染为常见诱因。部分患儿有直立不耐受家族史,且易伴有晕车经历。     

Growth Hormone Response to Overnight Growth Hormone-Releasing Hormone Infusion and Oral Pyridostigmine in Children with Short Stature

Ross, R.J.M., Savage, M.O., Kirk, J.M.W. and Besser, G.M. (Departments of Endocrinology and Child Health, St Bartholomew's Hospital, London, UK). Growth hormone response to overnight growth hormone-releasing hormone infusion and oral pyridostigmine in children with short stature. Acta Paediatr Scand [Suppl] 349: 114, 1989.
The development of a long-acting or depot preparation of growth hormone-releasing hormone (GHRH) may have many advantages over conventional treatment (with GH) of GH-deficient children. Pyridostigmine, an acetylcholinesterase inhibitor, has been shown to augment basal GH secretion and the GH response to GHRH in short children. It may thus provide adjuvant therapy to depot GHRH. The GH response to a nocturnal subcutaneous infusion of GHRH (1–29)NH₂ in doses of 5 and 10 pg/kg/hour was investigated in five short, slowly growing children. The effect of oral pyridostigmine 60 mg on nocturnal GH secretion and the GH response to a nocturnal infusion was also examined. The subcutaneous infusion of GHRH augmented pulsatile GH release in all five children. There was a dose-related response to subcutaneous GHRH for the GH area under the curve and mean GH pulse amplitude, but no change in the number of pulses. There was a significant rise in the mean baseline GH concentration during the GHRH infusion compared with placebo. Pyridostigmine had no effect on either basal or stimulated GH secretion.     

Pharmacokinetics of enprofylline administered intravenously and as a sustained-release tablet at steady state in children with asthma

The pharmacokinetics of enprofylline (3-propylxanthine) were studied in 10 children with asthma (mean age 7.9 years), after enprofylline 1 mg/kg given intravenously and after enprofylline 7.5 +/- 1.3 mg/kg given as a sustained-release tablet after 8 days of oral dosing twice daily. The mean +/- SD enprofylline serum elimination half-life was 1.06 +/- 0.20 hours, considerably shorter than the half-life reported in adults. The mean steady-state volume of distribution was 0.55 +/- 0.05 L/kg. The mean clearance rate was 0.44 +/- 0.06 L/hr/kg. The mean enprofylline serum concentration at steady state was 1.7 +/- 0.5 mg/L. The mean peak to trough ratio was 3.02 +/- 1.31. On the first and ninth study days, 87% +/- 8% and 90% +/- 16%, respectively, of the dose of enprofylline was recovered as unchanged drug in the urine. Enprofylline has a short half-life in children, but the sustained-release formulation provides stable serum concentrations and satisfactory relief of asthma throughout the 12-hour dosing interval.     

Physiologic neurocirculatory patterns in the head-up tilt test in children with orthostatic intolerance

Background: Orthostatic intolerance (OI) is a common clinical manifestation in clinical pediatrics. The head‐up tilt (HUT) table test is considered the standard of orthostatic assessment, but the physiologic neurocirculatory profile during HUT has not been fully realized in children with OI. The present study, therefore, was designed to investigate the physiologic patterns that occur during HUT in children with OI. Methods: Ninety children (56 girls; mean age, 11.6 ± 2.3 years) with OI underwent HUT under quiet circumstances. Blood pressure and heart rate were monitored simultaneously. Results: Forty‐nine children with OI (54.4%) had vasovagal response with HUT testing; 33 (36.7%), vasodepressor response; six (6.7%), cardioinhibitory response; and 10 (11.1%), mixed response. Twenty‐eight children (31.1%) had postural orthostatic tachycardia; one (1.1%), orthostatic hypotension (OH); and 12 (13.3%), normal physiologic response. Patterns of cerebral syncope response and chronotropic incompetence were not observed. Conclusions: Classical vasovagal response was the major physiologic pattern seen in children with OI during HUT testing, and postural orthostatic tachycardia response ranked second.     

Impaired postural cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance

OBJECTIVES: To measure postural changes in cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance. STUDY DESIGN: We studied 28 patients (age, 10 to 22 years) and 20 healthy control subjects (age, 6 to 27 years). Cerebral oxygenated hemoglobin (oxy-Hb) and deoxygenated Hb were noninvasively and continuously measured with near infrared spectroscopy during active standing. Beat-to-beat arterial pressure was monitored by Finapres. RESULTS: Orthostatic intolerance determined by cardiovascular responses to standing was observed in 16 of 28 patients: instantaneous orthostatic hypotension in 8, delayed orthostatic hypotension in 2, and postural orthostatic tachycardia in 6. A rapid recovery of oxy-Hb by near infrared spectroscopy at the onset of active standing was not found in 15 of 16 patients with chronic fatigue and orthostatic intolerance and in 6 of 12 patients with chronic fatigue without orthostatic intolerance but only in 2 of 20 control subjects. Thirteen of 16 patients with orthostatic intolerance showed prolonged reduction in oxy-Hb during standing. CONCLUSIONS: Impaired cerebral hemodynamics in patients with chronic fatigue syndrome and postural orthostatic tachycardia suggest a link between impaired cerebral oxygenation and chronic fatigue. However, this cannot explain the symptoms in patients meeting the criteria of chronic fatigue without orthostatic intolerance.     

Orthostatic intolerance in adolescent chronic fatigue syndrome

OBJECTIVES: To demonstrate the association between orthostatic intolerance and the chronic fatigue syndrome (CFS) in adolescents and to delineate the form that orthostatic intolerance takes in these children. STUDY DESIGN: We investigated the heart rate and blood pressure (BP) responses to head-up tilt (HUT) in 26 adolescents aged 11 to 19 years with CFS compared with responses in adolescents referred for the evaluation of simple faint and to responses in 13 normal healthy control children of similar age. RESULTS: A total of 4/13 of the controls and 18/26 simple faint patients experienced typical faints with an abrupt decrease in BP and heart rate associated with loss of consciousness. One CFS patient had a normal HUT. A total of 25/26 CFS patients experienced severe orthostatic symptoms associated with syncope in 7/25, orthostatic tachycardia with hypotension in 15/25, and orthostatic tachycardia without significant hypotension in 3/25. Acrocyanosis, cool extremities, and edema indicated venous pooling in 18/25. None of the control or simple faint patients experienced comparable acral or tachycardic findings. CONCLUSIONS: We conclude that chronic fatigue syndrome is highly related to orthostatic intolerance in adolescents. The orthostatic intolerance of CFS often has heart rate and BP responses similar to responses in the syndrome of orthostatic tachycardia suggesting that a partial autonomic defect may contribute to symptomatology in these patients.     

儿童体位性心动过速综合征的发病机制

体位性心动过速综合征是一种与体位有明确关系的窦性心动过速,特征性临床表现为当患者体位由平卧位转为直立时,于10 min内心率增加≥30次.min-1,或心率最大值≥120次.min-1。体位性心动过速的发病机制目前尚未明了,可能主要与中心血容量改变、自主神经及肌肉泵功能障碍、血管内皮功能异常以及基因变异等有关。     

���Ӷ�ͯ��������Ѫ�ܼ������廯ҽ��

??Pediatric functional cardiovascular diseases involve a series of dysfunctions which can affect children’s physical and mental health. They include vasovagal syncope??postural tachycardia syndrome??orthostatic hypotension??orthostatic hypertension and beta-adrenoceptor hyperfunction??etc. Since the above-mentioned diseases have various therapeutic response??with the research progress of the disease mechanisms and prognosis??great progress has been made in individualized management of pediatric functional cardiovascular diseases. In the future??great attention should be paid to the individualized diagnosis and treatment of the diseases so as to improve the diagnostic and therapeutic technology.     

Safety and pharmacokinetics of fluconazole in children with neoplastic diseases

To evaluate the safety, tolerance, and pharmacokinetics of fluconazole in children with neoplastic diseases, we studied fluconazole in 26 children, aged 5 to 15 years, with normal renal function who were receiving treatment for cancer. The patients received fluconazole, 2, 4, or 8 mg/kg per day for 7 days intravenously for a 2-hour period. Patients had no nausea or vomiting related to fluconazole; three patients had an asymptomatic rise in hepatic aminotransferase values after four to six doses (one patient at 2 mg/kg per day and two patients at 8 mg/kg per day), which returned to normal within 2 weeks after discontinuation of the drug. Fluconazole showed linear first-order kinetics over the dosage range tested and during multiple dosing. After the first dose, mean clearance was 22.8 +/- 2.3 ml/min, volume of distribution 0.87 +/- 0.06 L/kg, and terminal elimination half-life 16.8 +/- 1.1 hours. Similarly, after the last dose, clearance was 19.4 +/- 1.3 ml/min, volume of distribution 0.84 +/- 0.04 L/kg, and terminal elimination half-life 18.1 +/- 1.2 hours. Patients receiving their first fluconazole dose of 8 mg/kg achieved peak serum levels of 9.5 +/- 0.4 microgram/ml and trough levels of 2.7 +/- 0.5 microgram/ml 24 hours later, and an area under the serum concentration-time curve from time zero to infinity of 186 +/- 16 micrograms.hr per milliliter. Renal clearance of fluconazole was 65% +/- 5% of total clearance and demonstrated the predominantly renal excretion of this drug. We suggest that the shorter serum half-life and the higher frequency of aminotransferase elevations in comparison with those of adults warrant careful investigation of fluconazole in controlled clinical trials.     

���������Ƿ��ӵĶ�ͯѪ����������������λ���Ķ������ۺ����ٴ��������

??Vasovagal syncope??VVS?? and postural orthostatic tachycardia syndrome??POTS?? are the two common types of neurally mediated syncope in children. It is sometimes hard to identify the VVS from POTS merely depending on the symptoms. Studies of translational medicine recently have shown that the circulating biomarkers?? hydrogen sulfide??H2S?? and serum iron both have predict value in assessing the therapeutic efficacy and differentiating between VVS and POTS.     

Increased enoxaparin dosing is required for obese children

Weight-based dosing for enoxaparin is recommended in the 2008 American College of Chest Physicians (ACCP) guidelines for venous thromboembolism (VTE) prophylaxis. Enoxaparin 0.5 mg/kg per dose administered subcutaneously every 12 hours is recommended for this indication in children. There is no established upper dosing limit of enoxaparin for prophylaxis in children, and the US Food and Drug Administration-approved enoxaparin dose for adults for VTE prophylaxis is 30 mg subcutaneously every 12 hours or 40 mg subcutaneously daily. Therefore, we assumed that the upper limit for children is 40 mg subcutaneously daily. We reviewed 3 cases of obese adolescent boys who required large doses of enoxaparin to achieve the ACCP-recommended anti-factor Xa range of 0.1 to 0.3 IU/mL for the prevention of VTE. All 3 patients required doses of enoxaparin that are higher than that recommended for adults for VTE prophylaxis: patient A (BMI: 105.9) required >0.28 mg/kg per dose, patient B (BMI: 95.7) required 0.15 mg/kg per dose, and patient C (BMI: 29.9) required 0.49 mg/kg per dose. The desired anti-factor Xa range was achieved when enoxaparin was administered every 12 hours in each patient with no reported episodes of VTE. One patient had minor bruising, but no other adverse events were noted. Because of the variability in dose requirements and unpredictability in patient responses demonstrated in our 3 adolescents, prospective studies are needed to provide definitive recommendations on dosing of enoxaparin for VTE prophylaxis in this subset of obese pediatric patients.     

儿童体位性心动过速综合征合并血管迷走性晕厥的诊断探讨

目的：探讨儿童体位性心动过速综合征（POTS）合并血管迷走性晕厥（VVS）的诊断。方法：回顾性地复习2007年1月至2010年12月经直立倾斜试验（HUT）诊断为POTS的57例儿童的临床资料,其中男29例,女28例,年龄5～16(12.2±1.9)岁。结果：57例POTS儿童中,在可以耐受倾斜体位的前提下,通过延长HUT时间,24例(42%)经HUT诊断合并VVS,其中血管抑制型20例,混合型3例,心脏抑制型1例。合并VVS儿童平均年龄（13.0±1.4岁）大于未合并VVS的POTS儿童（11.5±2.1岁）,差异有统计学意义（P0.05）。结论：部分POTS儿童合并VVS,在可以耐受倾斜体位的前提下,延长HUT时间有利于防止VVS漏诊。与未合并VVS的POTS儿童比较,合并VVS儿童年龄较大,但性别、临床症状无明显差异。     

Japanese clinical guidelines for juvenile orthostatic dysregulation version 1

This clinical practice guideline provides recommendations for the assessment, diagnosis and treatment of school-aged children and juveniles with orthostatic dysregulation (OD), usually named orthostatic intolerance in USA and Europe. This guideline is intended for use by primary care clinicians working in primary care settings. The guideline contains the following recommendations for diagnosis of OD: (i) initial evaluation composed of including and excluding criteria, the assessment of no evidence of other disease including cardiac disease and so on; (ii) a new orthostatic test to determine four different subsets: instantaneous orthostatic hypotension, postural tachycardia syndrome, neurally mediated syncope and delayed orthostatic hypotension; (iii) evaluation of severity; and (iv) judgment of psychosocial background with the use of rating scales. The guideline also contains the following recommendations for treatment of OD on the basis of the result of an orthostatic test in addition to psychosocial assessment: (i) guidance and education for parents and children; (ii) non-pharmacological treatments; (iii) contact with school personnel; (iv) use of adrenoceptor stimulants and other medications; (v) strategies of psychosocial intervention; and (vi) psychotherapy. This clinical practice guideline is not intended as a sole source of guidance in the evaluation of children with OD. Rather, it is designed to assist primary care clinicians by providing a framework for decision making of diagnosis and treatments.     

Individualizing gentamicin dosage in patients with cystic fibrosis: limitations to pharmacokinetic approach

Gentamicin serum concentrations were measured in 15 children and seven adults with cystic fibrosis and in eight children with other diseases. Potentially toxic trough concentrations occurred in three of the first nine patients studied, in whom the dose and a 4-hour dosing interval were prescribed on the basis of one-compartment pharmacokinetic calculations (Sawchuck-Zaske method). In contrast, final concentrations were within the accepted target ranges for the remaining 13 patients with cystic fibrosis, in whom the dose and interval were adjusted empirically on the basis of a single pair of "peak" and trough values. The mean +/- SD final dosage required to achieve target concentrations was 13.8 +/- 2.9 mg/kg/d for children and 11.8 +/- 1.1 mg/kg/d for adults (P greater than 0.05), generally divided into four doses at 6-hour intervals. Mean half-life and incremental increase in serum concentration from previous trough to subsequent "peak," an indirect measurement of volume of distribution, were not significantly different between children or adults with cystic fibrosis and pediatric control subjects; there was little interpatient variability in these values. Thus the high dosage requirements were related more to the higher target concentrations than to altered pharmacokinetic disposition in patients with cystic fibrosis. We conclude that the initial dose of gentamicin to achieve a peak of 8 to 12 micrograms/mL and a trough of less than 2.0 micrograms/mL in patients with cystic fibrosis should be 3 mg/kg administered every 6 hours in children and every eight hours in adults. Subsequent dosage adjustment should be made on the basis of a pair of peak and trough serum concentration measurements obtained after the fifth dose. Dosing intervals in this patient population generally should be no shorter than every 6 hours, even if the initial trough concentration is less than 1 microgram/mL.     

Pediatric autonomic testing: retrospective review of a large series

OBJECTIVE. To describe the reasons for referral, autonomic diagnoses, test results, and patient management in a large pediatric population referred for testing for an autonomic disorder. DESIGN. The authors reviewed autonomic testing data and medical records for patients aged 18 years and younger who underwent testing between 1993 and 2007 and who had adequate clinical data. Relevance of test results to clinical symptoms was ranked on a 3-point scale. Treatments were noted and their benefit ranked on a 5-point scale. RESULTS. Among 142 pediatric patients identified, postural tachycardia syndrome was most common (71%) while orthostatic hypotension was rare (5%). Testing provided relevant information regarding the patient's symptoms in 88% of the cases. Beta-blockers were the most commonly prescribed medication (59%); 73% improved. CONCLUSIONS. Postural tachycardia syndrome was common in this large pediatric population, whereas orthostatic hypotension was infrequent. The symptomatic improvement in the majority bears an unclear relationship to treatment. Prospective studies are needed.     

Comparison of carboplatin pharmacokinetics between an anephric child and two children with normal renal function

Carboplatin, a promising second generation platinum compound, is an effective antitumor drug and appears to be less nephrotoxic than cisplatin. We report comparative pharmacokinetics of carboplatin in an anephric child and two children with normal renal function. All three children were infused with carboplatin over 4 hours, the anephric child receiving 100 mg/m² (25% of the dose received by the other two children). This dose was well tolerated and 18 days later the anephric patient received a second course of carboplatin at 50% of the regular dose received by the control patients. Following this dose the girl experienced severe pancytopenia and recovered with the use of GM-CSF, blood, and platelet transfusion. Blood samples were obtained at timed intervals for 24 hours in the control subjects and for 40 hours in the anephric patient. Plasma and plasma ultrafiltrates were analyzed for total and free platinum. The results show that elimination half-life of total platinum was 13 hours in the children with normal renal function and 42 hours in the anephric child following the 100 mg/m² dose. The elimination T_1/2 of free platinum was 8 hours in a child with normal GFR and 32 hours in the anephric child. In the anephric child the clearance of ultrafiltrable platinum was 10% of the normal total body clearance. We suggest that, in children with renal insufficiency, the dose of platinum derivatives should be carefully chosen, proportionally to the degree of renal impairment. © 1993 Wiley-Liss, Inc.     

��ͯѪ�����������ʼ���λ�� �Ķ������ۺ����ٴ���������

目的探讨鉴别血管迷走性晕厥(VVS)及体位性心动过速综合征(POTS)的临床依据。方法 2009年4月至2011年4月于北京大学第一医院儿科门诊就诊并确诊为VVS的儿童40例,年龄6～18岁,平均(11.8±2.9)岁;POTS儿童165例,年龄5～19岁,平均(11.4±2.7)岁。评价与检查手段包括临床表现、家族史、生活习惯、直立试验以及直立倾斜试验。结果 VVS和POTS在儿童时期的共同特征包括学龄期及青春期多发、女孩稍多于男孩、发作季节以夏秋季多见、多数患儿有诱因和发作先兆、发作后仍有不适、平卧后症状可缓解。在VVS儿童中以晕厥为主要表现者明显多于POTS(P<0.001),在POTS儿童中,以头晕为表现的患儿明显多于VVS(P<0.001)。VVS患儿中父方有直立不耐受家族史者明显多于POTS患儿(P<0.05)。结论直立倾斜试验是鉴别VVS与POTS的重要客观检查手段。晕厥及头晕的发生频率对于临床鉴别诊断VVS与POTS具有参考价值。