Albuterol overdose: a case report and differential diagnosis.

The increase in the use of selective beta 2 agonists as first-choice agents in the therapy of asthma has resulted in a concomitant increase in overdoses and other therapeutic misadventures. This case describes a 22-month-old child who ingested a large overdose of albuterol, resulting in an acute syndrome consisting of agitation, tremulousness, marked hyperglycemia of > 320 mg/dl (17.8 mmol/L), ketonuria, and hypokalemia. Such toxicity has generally been reported only in diabetics or pregnant patients. These findings and a brief review of the pharmacology and toxicology of beta 2 agonists are detailed, with special emphasis on the differential diagnosis of overdoses characterized by hyperglycemia, hypokalemia, agitation, and tremulousness. A system of ordering the relative toxicity of these (and other) drugs is proffered using the exposure-case fatality rate (ECFR) as a crude measure of clinical toxicity (while delineating its shortcomings). Applying the ECFR (using American Association of Poison Control Centers' data base) to beta 2 agonist overdoses indicates that the resulting clinical syndrome, while troublesome, generally results in a benign outcome.     

Acute thyroxine ingestion in pediatric patients

During a 1-year period, 15 cases of acute thyroxine (T4) overdose with documented serum T4 concentrations were studied. All patients were less than 5 years of age and 80% were boys. All were examined within 1 to 6 hours of ingestion and all were asymptomatic. Estimated dose ingested in 10 patients ranged from 1.5 to 8.8 mg (0.1 to 0.73 mg/kg). Three patients with initial T4 serum concentrations greater than 75 micrograms/dL manifested signs of toxicity within 12 to 48 hours (fever, tachycardia, hypertension, and/or agitation) that resolved within 24 to 60 hours. The mean elimination half-life of T4 in 7 patients with multiple serum concentrations was 2.8 +/- 0.4 days, whereas the mean elimination half-life of triiodothyronine was 6 +/- 1.7 days. It was concluded that (1) the majority of acute pediatric T4 overdoses are not severe and may be managed on an outpatient basis, (2) the absence of early clinical manifestations does not preclude delayed onset of toxicity that may be better predicted by initial T4 concentrations, and (3) the elimination half-life of T4 is shorter and the elimination half-life of tri-iodothyronine is longer than with therapeutic doses.     

Persistent hyperglycemia in critically ill children

OBJECTIVES: To determine the prevalence and prognostic significance of hyperglycemia among critically ill nondiabetic children. STUDY DESIGN: We performed a retrospective cohort study using point-of-care blood glucose measurements, hospital administrative databases, and a computerized information system; 942 nondiabetic patients admitted to our Pediatric Intensive Care Unit (PICU) from October 2000 to September 2003 were included. The prevalence of hyperglycemia was based on initial PICU glucose measurement, highest value within 24 hours, and highest value measured during PICU stay up to 10 days after the first measurement. Primary outcome was in-hospital death with PICU lengths of stay (LOS) as secondary outcome. RESULTS: Through the use of three cutoff values (120 mg/dL, 150 mg/dL, and 200 mg/dL), the prevalence of hyperglycemia was 16.7% to 75.0%. The relative risk (RR) for dying increased for maximum glucose within 24 hours >150 mg/dL (RR, 2.50; 95% confidence interval (CI), 1.26 to 4.93) and highest glucose within 10 days >120 mg/dL (RR, 5.68; 95% CI, 1.38 to 23.47). LOS was decreased for admission glucose >120 mg/dL and 150 mg/dL but increased for all threshold values for maximum glucose within 10 days. CONCLUSIONS: Hyperglycemia occurs frequently among critically ill nondiabetic children and is correlated with a greater in-hospital mortality rate and longer LOS.     

Baclofen overdose: drug experimentation in a group of adolescents

BACKGROUND: Baclofen, a lipophilic analog of gamma-aminobutyric acid, is clinically used to control spasticity. We report a mass exposure to baclofen in adolescents seeking intoxication; toxicokinetic data are included. CASE SERIES: A group of adolescents became symptomatic after ingesting 3 to 30 20-mg tablets of baclofen during a party at a suburban Boys' Club. Several children were noted to be very lethargic by chaperones, ingestion was suspected, and paramedics were called. Some white tablets were found in a couch at the site of the party. The Massachusetts Poison Control Center was called, and the tablets were identified as baclofen (20 mg). Fourteen patients were taken to local hospitals; 9 required intubation. Eight adolescents were transferred to our institution. In these 8 patients, symptoms were noted within 1 to 2 hours after overdose. The most common clinical findings included coma (7), hypothermia (6), bradycardia (5), hypertension (4), and hyporeflexia (8). Mean length of mechanical ventilation was 40 hours. Three patients had unifocal premature ventricular contractions. Two patients had tonic-clonic seizures. A single dose of activated charcoal was given to all patients. Drugs administered included nifedipine (1), flumazenil (1), naloxone (1), lorazepam (2), and phosphenytion (2). All patients recovered and were discharged home within 5 days of ingestion. Serial serum baclofen levels were obtained in all intubated patients (range, 0.049 to 6.0; normal, 0.08 to .40 microgram/mL). Levels obtained 14 hours after ingestion showed a linear correlation with length of mechanical ventilation (R2 = 0.9863). Persistent symptoms were noted in some patients, despite nondetectable baclofen levels. Toxicologic screening for drugs of abuse was negative except in 2 patients with ethanol levels, both < 5 mg/dL. CONCLUSION: Baclofen overdose may result in coma, apnea, autonomic disturbances, cardiac conduction abnormalities, and seizures. Levels obtained shortly after overdose correlate with length of mechanical ventilation.     

A protocolized approach to identify and manage hyperglycemia in a pediatric critical care unit

INTRODUCTION: Hyperglycemia is a risk factor for poor outcome in critically ill patients, and glycemic control may decrease morbidity and mortality in adults. There is limited information regarding hyperglycemia and its control in pediatric intensive care. OBJECTIVE: To determine prevalence and risk factors for hyperglycemia and evaluate our approach to glycemic control in critically ill children. DESIGN, SETTING, PATIENTS, AND MAIN OUTCOMES: A pediatric-specific protocol to identify and manage hyperglycemia was developed and instituted as standard practice in our pediatric intensive care unit, and was applicable to patients >6 months and >5 kg, without end-stage liver disease or type 1 diabetes mellitus. Triggers for routine blood glucose assessment were based on supportive measures including mechanical ventilation, vasopressor/inotrope infusions, and antihypertensive infusions. Hyperglycemic patients, defined by two consecutive blood glucose readings of >140 mg/dL (7.7 mmol/L), were treated with infused insulin to maintain blood glucose levels 80-140 mg/dL (4.4-7.7 mmol/L). We performed retrospective analysis 6 months after instituting this approach. Main outcomes were prevalence and risk factors for hyperglycemia, and effectiveness of our approach to achieve glycemic control. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: One hundred forty-five of 477 patients had blood glucose actively assessed, and 74 developed hyperglycemia and were managed with insulin. This approach to identify patients with hyperglycemia had a positive predictive value of 51% and negative predictive value of 94%. Hyperglycemia prevalence was 20%. Mechanical ventilation, vasopressor/inotropic infusion, continuous renal replacement therapy, high illness severity scores, and longer lengths of stay were associated with hyperglycemia. The average blood glucose of patients with hyperglycemia was 200 mg/dL (11 mmol/L), and on average, patients were treated with insulin for 6.3 days with 2.4 units/kg/day. Blood glucose levels were <160 mg/dL (8.8 mmol/L) in 70% of insulin-treated days, 80-140 mg/dL (4.4-7.7 mmol/L) in 49% of insulin-treated days, and 4% of insulin-treated patients had any blood glucose measurements <40 mg/dL (2.2 mmol/L). CONCLUSIONS: Hyperglycemia is prevalent in pediatric intensive care units and may be effectively identified and managed using a protocolized approach.     

Detection of phenylketonuria in the very early newborn blood specimen

Early hospital discharge of newborns is leading to collection of the newborn screening blood specimen during the first day of life in increasing numbers of newborns. There is concern that neonates with phenylketonuria who are tested this early may be missed. To examine this question, the authors screened specimens collected during the first 24 hours of life from 23 neonates at risk for hyperphenylalaninemia. The blood phenylalanine level in each of the 6 neonates with phenylketonuria and a seventh with mild hyperphenylalaninemia was greater than 2 mg/dL as early as 4 hours of age and 6 mg/dL or greater by 24 hours of age. A newborn screening phenylalanine cutoff level of 2 mg/dL would have identified all of these neonates within the first 24 hours of life, but a cutoff level of 4 mg/dL would have missed 2 of the 6 with phenylketonuria before 24 hours of life. Newborn screening programs should adopt a blood phenylalanine level of 2 mg/dL as the cutoff for suspicion of phenylketonuria and request for a second specimen. Breast-fed affected neonates had higher early blood phenylalanine elevations than formula-fed neonates, perhaps reflecting the higher protein (phenylalanine) content of colostrum.     

Predicting concentrations in children presenting with acetaminophen overdose.

OBJECTIVE: To predict serum concentrations to evaluate and improve guidelines for the treatment of children (1 to 5 years) with accidental ingestion of acetaminophen elixir. METHODS: Acetaminophen concentrations for 1000 children were simulated with pharmacokinetic parameters and their expected variability. The distribution of concentrations arising from a 300 mg/kg dose at different age groups was predicted. These predictions were validated by comparison with concentrations obtained at 4 hours from 121 children with accidental ingestion of acetaminophen elixir. RESULTS: No child who presented with overdose had a concentration in the probable risk area of the Rumack-Matthew toxicity nomogram. Enteral charcoal administered 98 minutes (SD 44) after ingestion had no effect on serum concentrations. The simulation predicted that an acetaminophen dose of 300 mg/kg would result in concentrations of 32 to 208 mg/L (95% CI) at 4 hours after ingestion. The maximum concentration occurred before 2 hours in 95% of simulated children. CONCLUSION: Children (1 to 5 years) with reported ingestion of >250 mg/kg acetaminophen elixir should have serum concentrations measured at 2 hours after ingestion rather than at the 4-hour time point recommended in adults. This can be expected to speed discharge and reduce anxiety. The use of enteral charcoal is unlikely to enhance acetaminophen elimination, unless it is given within an hour of acetaminophen ingestion.     

Association of timing, duration, and intensity of hyperglycemia with intensive care unit mortality in critically ill children.

OBJECTIVE: To study the association of timing, duration, and intensity of hyperglycemia with pediatric intensive care unit (PICU) mortality in critically ill children. DESIGN: Retrospective cohort study. SETTING: PICU of a university-affiliated, tertiary care, children's hospital. PATIENTS: A total of 152 critically ill children receiving vasoactive infusions or mechanical ventilation. INTERVENTIONS: None. METHODS: With institutional review board approval, we reviewed a cohort of 179 consecutive children, 1 mo to 21 yrs of age, treated with mechanical ventilation or vasoactive infusions. We excluded 18 with <3 microg.kg(-1).min(-1) dopamine only, diabetes, or solid organ transplant and nine who died within 24 hrs of PICU admission. Peak blood glucose (BG) and time to peak BG during PICU admission, duration of hyperglycemia (percentage of PICU days with any BG of >126 mg/dL), and intensity of hyperglycemia (median BG during first 48 PICU hours) were analyzed for association with PICU mortality using chi-square, Student's t-test, and logistic regression. MEASUREMENTS AND MAIN RESULTS: Peak BG of >126 mg/dL occurred in 86% of patients. Compared with survivors, nonsurvivors had higher peak BG (311 +/- 115 vs. 205 +/- 80 mg/dL, p <.001). Median time to peak BG was similar in nonsurvivors (23.5 hrs; interquartile ratio, 5-236 hrs) and survivors (19 hrs; interquartile ratio, 6-113 hrs). Duration of hyperglycemia was longer in nonsurvivors (71% +/- 14% of PICU days) vs. survivors (37% +/- 5% of PICU days, p <.001). Nonsurvivors had more intense hyperglycemia during the first 48 hrs in the PICU (126 +/- 38 mg/dL) vs. survivors (116 +/- 34 mg/dL, p <.05). Univariate logistic regression analysis showed that peak BG and the duration and intensity of hyperglycemia were each associated with PICU mortality (p <.05). Multivariate modeling controlling for age and Pediatric Risk of Mortality scores showed independent association of peak BG and duration of hyperglycemia with PICU mortality (p <.05). CONCLUSIONS: Hyperglycemia is common in critically ill children. Peak BG and duration of hyperglycemia are independently associated with mortality in our PICU. A prospective, randomized trial of strict glycemic control in this subset of critically ill children who are at high risk of mortality is both warranted and feasible.     

Accuracy of glucose reflectance testing for detecting hypoglycemia in term newborns

Glucose concentrations of 248 newborns at 1 and 3 hours of age were determined at the bedside by means of the Accu-Chek III Reflectance meter and in the laboratory by means of the Vitros 750 analyzer. Hypoglycemia being defined as a glucose concentration less than 40 mg/dL, the reflectance meter had a sensitivity of 0.757 and a specificity of 0.876 at 1 hour and 0.975 at 3 hours. The imprecision of the reflectance meter at 1 hour eliminated it as a routine testing method.     

Survival after first esophageal variceal hemorrhage in patients with biliary atresia

OBJECTIVE: To determine the influence of the new onset of esophageal variceal hemorrhage (EVH) on transplant-free survival in children with biliary atresia and to examine variables that predicted survival after the onset of EVH. METHODS: Retrospective chart review of 134 patients with biliary atresia who underwent portoenterostomy between 1973 and 1992 at a single institution; 29% had EVH. RESULTS: The risk of death or need for liver transplantation was 50% at 6 years after the initial episode of EVH. Patients with a serum bilirubin concentration < or =4 mg/dL at the first episode of EVH had transplant-free survival of >80% for 4 years after this episode, those with bilirubin levels >4 to 10 mg/dL had 50% survival at 1 year, and those with bilirubin levels >10 mg/dL had 50% survival at 4 months. The risk of death or transplant for a child with EVH and total serum bilirubin levels >10 mg/dL was 12.0 (95% CI: 6.0, 24.1), 4 to 10 mg/dL was 7.2 (3.1, 16.7), and < or =4 mg/dL was 0.6 (0.1, 3.1) times the risk of a same-aged child who did not have EVH. CONCLUSIONS: Children with biliary atresia and first EVH episode have a variable prognosis related to total serum bilirubin concentration at the time of the episode.     

Jaundice noted in the first 24 hours after birth in a managed care organization

OBJECTIVE: To investigate the significance of jaundice noted in the first 24 hours after birth in a community setting. DESIGN: Supplementary analyses of a nested case-control study. SETTING: Northern California Kaiser Permanente Medical Care Program. PATIENTS: Six hundred thirty-one randomly selected newborns (controls) and 140 cases with total serum bilirubin levels of 25 mg/dL (428 micro mol/L) or higher from a cohort of 105 384 newborns of at least 2000 g birth weight and at least 36 weeks' gestational age, born between January 1, 1995, and December 31, 1998. MAIN OUTCOME MEASURES: Notations of jaundice in the medical record, timing and results of bilirubin testing, use of phototherapy, and development of bilirubin levels of 25 mg/dL or higher. RESULTS: Among the controls, the cumulative probability of a notation of jaundice (corrected for early hospital discharge using survival analysis) was 2.8% within 18 hours and 6.7% within 24 hours. In these newborns, cumulative proportions that had bilirubin levels measured were 38% within 12 hours and 43% within 24 hours of when jaundice was first noted. About 40% of bilirubin levels measured within 24 hours were above the estimated 95th percentile for age. Compared with newborns not noted to be jaundiced on the first day, newborns noted to be jaundiced within 24 hours were more likely to receive phototherapy (18.9% vs 1.7%; relative risk, 10.1; 95% confidence interval, 4.2-24.4) and to develop a bilirubin level of 25 mg/dL or higher (odds ratio, 2.9; 95% confidence interval, 1.6-5.2), but the absolute risk increase for total serum bilirubin levels of 25 mg/dL or higher was 0.2%. CONCLUSION: Jaundice noted in the medical record in the first 24 hours after birth was uncommon and often clinically significant in this setting, but other factors also need to be considered in determining its importance.     

Screening for hypoglycemia in exclusively breastfed high-risk neonates

Objective

To determine incidence of hypoglycemia in exclusively breastfed, high-risk but healthy newborns, and risk factors for its development.

Methods

This observational study enrolled 407 exclusively breastfed high-risk (low birth weight newborns (1800-2499 g), late preterms, small-for-gestation, large-for-gestation and infant of diabetic mother), who did not require admission to neonatal intensive care unit and were kept in postnatal wards with mother. Hypoglycemia was defined as blood glucose ≤46 mg/dL (2.6 mmol/L). Blood glucose was monitored till 48 hours of life.

Results

27% of the screened newborns developed hypoglycemia in first 48 hours. 31 (7.6%) developed recurrent (>2) episodes, 28 (6.8%) had moderate (<37mg/dL) while 8 (1.9%) developed symptomatic hypoglycemia. With increase in birthweight, risk of hypoglycemia reduced significantly (P=0.003). Hypoglycemia was observed more frequently in first 2 hours as compared to next 48 hours (P=0.0001). Low birth-weight, preterm gestation and male gender was significantly associated with increased risk of hypoglycemia.

Conclusion

Healthy, high-risk exclusively breastfed newborns in postnatal wards need close monitoring for hypoglycemia in first 24 hrs of life.

     

Hypoglycemia in the newborn

Hypoglycemia in a neonate has been defined as blood sugar value below 40mg/dL. Hypoglycemia is encountered in a variety of neonatal conditions including prematurity, growth retardation and maternal diabetes. Screening for hypoglycemia in certain high-risk situations is recommended. Supervised breast-feeding may be an initial treatment option in asymptomatic hypoglycemia. However, symptomatic hypoglycemia should always be treated with a continuous infusion of parenteral dextrose. Neonates needing dextrose infusion rates above 12 mg/Kg/min should be investigated for the cause of hypoglycemia. Hypoglycemia has been linked to poor neuro-developmental outcome, and hence aggressive screening and treatment is recommended.     

Low-dose intravenous insulin in the treatment of diabetic ketoacidosis.

Continuous slow intravenous infusion of insulin was used in 52 episodes of diabetic ketoacidosis. No complications of therapy, ie, hypoglycemia, induced hypokalemia, insulin resistance, or cerebral edema, were encountered. Potassium phosphate was given to 47 of the 52 patients. Sodium bicarbonate was administered to only one patient. The hyperglycemia frequently resolved more rapidly than the systemic acidosis; this was managed by adding glucose to the intravenous fluids when the blood sugar concentration decreased to approximately 250 mg/dL; insulin infusion, however, was continued until the acidosis was corrected (venous standard bicarbonate greater than 14 mEq/L). We have found this method of treatment to be safe and simple to administer, and we believe it is the preferred treatment of patients with diabetic ketoacidosis.     

Newborn screening for phenylketonuria: predictive validity as a function of age

Data from questionnaires were assembled for 109 infants with phenylketonuria (PKU) and 114 control infants to assess the predictive validity of newborn screening for PKU as a function of age. Patients with PKU had values of less than 4 mg/dL in cord blood and in samples from days 1, 2, and 4 through 7. The proportion of patients with PKU expected to fall below screening cutoffs of 2, 4, and 6 mg/dL was predicted for each age range. Using a cutoff of 4 mg/dL, approximately one third of patients with PKU would be missed by a sample taken from the neonate in the first 12 hours of life, and nearly 10% would be missed with a sample from the second 12 hours of life. This study shows that not all patients with PKU will be detected by newborn screening, and that the phenomenon of early nursery discharges must be considered in developing appropriate screening strategies.     

Value of the intravenous route for the use of phenobarbital in asphyxiated full term newborn infants

Phenobarbital (20 mg/kg) was given intravenously to asphyxiated full term neonates who were less than 48 hours old. Further doses were given for 4 days (5 mgs/kg/d). Plasma levels were within the therapeutic range from 5 to 36 hours after the first injection but the maintenance dose always resulted in overdose by 5th day. The exact maintenance dose needs to be determined.     

GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY AND GILBERT SYNDROME

The authors describe the paradoxical clinical phenotype of an undetected severe hemolysis in parallel with the development of severe jaundice in a 13-year-old male suffering from a confirmed interaction of glucose-6-phosphate dehydrogenase deficiency (Mediterranean variant, 563 C/T) and Gilbert syndrome [variant (TA)7/(TA)7]. The child had 2 acute hemolytic episodes at the age of 10 and 13 years following infections of unknown origin. Both episodes were characterized by considerably high bilirubin levels (1st episode: 10.8 mg/dL, 2nd episode: 17.8 mg/dL) associated with unexpectably mild hemolysis indices (1st episode hemoglobin levels, 11.1 g/dL; reticulocyte counts, 2.5%; 2nd episode hemoglobin values, 12.7 g/dL; reticulocyte counts, 2.5%). During the steady-state condition of the child, hemoglobin values were within the normal ranges for his age (14.2 g/dL) and bilirubin levels were slightly elevated (1.70 mg/dL, indirect 1.5 mg/dL). The interaction of the two genetic abnormalities in the causation of this odd clinical phenotype is discussed.     

Glucose-6-phosphate dehydrogenase deficiency and Gilbert syndrome: a gene interaction underlies severe jaundice without severe hemolysis

The authors describe the paradoxical clinical phenotype of an undetected severe hemolysis in parallel with the development of severe jaundice in a 13-year-old male suffering from a confirmed interaction of glucose-6-phosphate dehydrogenase deficiency (Mediterranean variant, 563 C/T) and Gilbert syndrome [variant (TA)7/(TA)7]. The child had 2 acute hemolytic episodes at the age of 10 and 13 years following infections of unknown origin. Both episodes were characterized by considerably high bilirubin levels (1st episode: 10.8 mg/dL, 2nd episode: 17.8 mg/dL) associated with unexpectably mild hemolysis indices (1st episode hemoglobin levels, 11.1 g/dL; reticulocyte counts, 2.5%; 2nd episode hemoglobin values, 12.7 g/dL; reticulocyte counts, 2.5%). During the steady-state condition of the child, hemoglobin values were within the normal ranges for his age (14.2 g/dL) and bilirubin levels were slightly elevated (1.70 mg/dL, indirect 1.5 mg/dL). The interaction of the two genetic abnormalities in the causation of this odd clinical phenotype is discussed.     

Increased cerebral blood flow and plasma epinephrine in hypoglycemic, preterm neonates

Cerebral blood flow, plasma epinephrine, and plasma norepinephrine were measured in 25 spontaneously breathing, preterm neonates (mean gestational age 30.4 weeks) 2 hours after birth, during a routine screening for low blood glucose levels. Increased cerebral blood flow and plasma epinephrine values were observed when blood glucose levels were low, whereas plasma norepinephrine was constant throughout the blood glucose range. Hypoglycemia (defined as blood glucose concentration less than 30 mg/dL) was found in 13 neonates who were treated with intravenous glucose and milk enterally. Blood glucose levels were normal in the remaining 12 control neonates who received milk by a gastric line. Approximately 30 minutes after treatment with intravenous glucose and/or milk, cerebral blood flow had decreased by a mean of 11.3% in the 13 hypoglycemic neonates but was still 37.5% higher than cerebral blood flow in the control neonates despite normalization of plasma epinephrine concentration. Mean arterial blood pressure and blood gas values were identical between groups throughout the investigation. It is suggested that a normal coupling between cerebral metabolic demands and flow is present in very preterm neonates and that epinephrine may play a role in the cerebral hyperperfusion. Although none of the neonates had clinical signs of hypoglycemia, the data suggest that counterregulatory mechanisms are invoked when blood glucose values are less than 30 to 45 mg/dL.     

儿童急性盐酸克仑特罗中毒临床特征分析及救治

目的：分析儿童急性盐酸克仑特罗中毒的临床特点、救治方法与效果,为临床及时认识和早期诊治提供依据。方法：对2011年4月住院的28例急性盐酸克仑特罗中毒患儿的临床资料进行回顾性分析。结果：28例患儿中,男15例,女13例,年龄1至13岁（平均年龄7±5岁）。中毒后主要表现为呕吐、心悸、肢体抖动等;血生化改变主要为低血钾、高乳酸血症、高血糖、血肌酸激酶增高等,心电图改变主要为窦性心动过速和S-T段下移。经使用β受体阻滞剂及补钾、护心等处理后,患儿在12~78 h后症状逐渐缓解。入院后48 h后血生化指标得到明显改善,5 d后全部痊愈出院。随访半个月无复发。结论:儿童急性盐酸克仑特罗中毒以呕吐、心悸、肢体抖动、低血钾、高乳酸血症、心动过速为主要特征。早期积极采取有效的抢救措施可提高救治成功率。