Medicolegal Issues

Pediatric Special Section


 

Meningococcal Disease in Peds

By J. Christopher Day, MD

Thompson, MJ, Ninis N, Perera R, et al. Clinical recognition of meningococcal disease in children and adolescents. Lancet. 2006 Feb 6;367(9508)397-403.

Data from medical records and parental questionnaires were examined to determine the time course and prevalence of signs and symptoms in meningococcal disease (sepsis and meningitis) in 448 children in Wales, England, and Northern Ireland.

The authors note that classic clinical features of the disease appear late in the illness. The symptoms that appear earliest (fever, poor feeding, nausea, vomiting, coryza, sore throat) are very non-specific, but somewhat later symptoms of sepsis including leg pains, cold hands and feet, and abnormal skin color appear before the classical clinical features in 72% of the children studied. The authors hope that recognition of these features can lead to earlier diagnosis and treatment of this severe disease.

Outcomes compared with placebo included a reduction in hospital stay from 5.7 weeks to 2.6 weeks; a reduction in the mean duration of intensive care by 3.2 weeks; the mean duration of mechanical ventilation by 2.6 weeks; the mean duration of tube or intravenous feeding by 6.4 weeks; and the mean hospital charges per patient by $88,600.

Treatment of Infant Botulism

Arnon SS, Schechter R, Maslanka SE, et al. Human botulism immune globulin for the treatment of infant botulism. N Engl J Med. 2006 Feb 2;354((5):462-471.

This is is a report of a randomized, double-blind, placebo controlled trial of the use of human botulism immune globulin intravenous (BIG-IV) used for the treatment of infant botulism. The study was performed on 122 infants with (initially) suspected and (later) laboratory confirmed infant botulism. BIG-IV was given within three days of hospital admission. The authors also performed an open-label study of 382 laboratory confirmed cases. Some of these began treatment as late as 18 days after hospital admission.

In the randomized trial, outcomes compared with placebo included a reduction in hospital stay from 5.7 weeks to 2.6 weeks (P<0.001); a reduction in the mean duration of intensive care by 3.2 weeks (P<0.001); the mean duration of mechanical ventilation by 2.6 weeks (P= 0.01); the mean duration of tube or intravenous feeding by 6.4 weeks; and the mean hospital charges per patient by $88,600 (P<0.001).

The only notable adverse event perhaps related to treatment was a transient blush-like erythematous rash. In the open-label study, treatment given within three days of hospital admission shortened the mean length of stay by approximately one week more than did treatment given four to seven days after admission. BIG-IV is now licensed as BabyBIG. The authors recommend treatment as soon as possible after hospital admission.—JCD

One of the goals of the study was to determine variables useful in distinguishing patients who would require subsequent in patient admission from those who would be discharged home from the observation unit. No such variables were found.

Eczema: Wet Wraps Versus Conventional Treatment

Hindley D, Galloway G, Murray J, et al. A randomised study of “wet wraps” versus conventional treatment for atopic eczema. Arch Dis Child. 2006 Feb;91(2):164-168.

The authors were interested in comparing the efficacy and parent perception of ease of application of conventional treatment (emulsifying ointments and topical steroids) with wet wraps (tubular retention bandages applied wet as occlusive dressings over emulsifying ointments) and topical steroids for exacerbations of eczema.

Fifty children were enrolled and randomized to either treatment group. Treatment was continued and patients were followed for one month. The change in eczema severity was scored using a previously published scale (SCORAD) for assessing severity. No differences were noted between the two groups, though the study had a number of limitations including use of only one potency of steroid (1% hydrocortisone) limiting generalizability, the length of treatment (regimens vary in length), and patient drop-outs (five dropped out—all in the wet wrap group).

Parents felt wet wraps were harder to use. The authors do note that there may be clinical situations (they mention short term treatment of acute erythrodermic eczema) where wet wraps are a useful option. There appear to be no advantages in the group studied over a four-week period and the disadvantages likely include parental perception of difficulty of use and a possibility of increased skin infections.—JCD

Mast cell activation and leukotriene secretion is present in a wheezing infant as noted by increased U-PGF2 and U-LTE4 levels, respectively.

A Study of Dehydrated Peds

Mallory MD, Kadish H, Zebrack M, Nelson D. Use of a pediatric observation unit for treatment of children with dehydration caused by gastroenteritis. Pediatr Emerg Care. 2006 Jan;22(1):1-6.

A case-control study was performed to examine 467 admissions to an observation unit in patients with dehydration from vomiting or diarrhea from presumed gastroenteritis. Patients were presumably admitted to the observation unit (staffed by emergency department personnel) if they were believed to require more rehydration than could be reasonably offered in the emergency department itself.

Controls were defined as those patients able to be discharged home from the observation unit within 24 hours and cases as those patients that required subsequent inpatient admission. Nineteen percent of the patients studied required inpatient admission.

One of the goals of the study was to determine variables useful in distinguishing patients who would require subsequent inpatient admission from those who would be discharged home from the observation unit. No such variables were found.

Variables studied included oral intake prior to presentation, urine output at presentation, symptoms at presentation (vomiting versus diarrhea versus both), predominant symptoms (vomiting versus diarrhea versus no predominance), duration of symptoms, abdomen tender to palpation (yes/no), previous visit within five days (yes/no), age, vital signs, bicarbonate levels, and mean sodium levels.—JCD

Routine Neuroimaging: Little Value When Evaluating Febrile Seizures

By Stevie Wilson, RN, CPNP

Teng D, Dayan P, Tyler S, et al. Risk of intracranial pathologic conditions requiring emergency intervention after a first complex febrile seizure episode among children. Pediatrics. 2006;117(2):304-308.

Febrile seizures occur in up to 5% of all children. One-third of febrile seizures are classified as complex (i.e., having multiple seizures, prolonged duration, or focal seizures). Complex febrile seizures have been associated with an increased risk of recurrent febrile seizures and epilepsy. However, they have not been associated with pathologic intracranial lesions that require emergency surgical intervention.

Previous studies suggest that intracranial abnormalities are rare among simple febrile seizures. The American Academy of Pediatrics (AAP) recommends against the use of neuroimaging with simple seizures, however, practice guidelines for emergency neuroimaging for complex seizures do not exist. The objective of this study was to determine the likelihood of a significant intracranial condition requiring emergency intervention in children with the first complex febrile seizure.

A retrospective review of prospectively collected data was performed for 71 children who presented to the pediatric emergency department after a first complex febrile seizure. None of the 71 patients had a pathologic intracranial lesion that required emergency intervention. The authors therefore concluded that the risk of pathologic intracranial conditions requiring emergency intervention is low, suggesting that routine emergency neuroimaging for this population is unnecessary.

Because methadone’s three-dimensional structure shares similarities with calcium channel antagonists, bradycardia may occur—especially at higher doses. This effect has been reported in the adult literature; however, this is the first report in an infant.

Managing Bronchiolitis above Sea Level

Choudhuri JA, Ogden LG, Ruttenber JA, et al. Effect of altitude on hospitalizations for respiratory syncytial virus infection. Pediatrics. 2006;117(2):349-356.

This interesting study sought to evaluate the effect altitude has on hospitalizations for RSV infection. A multivariate analysis was obtained and suggests that the rate of hospitalization for RSV increased by 25% among infants who were younger than one year of age for every 1,000 meters of altitude. The risk of RSV-associated hospitalization was highest at elevations above 2,500 meters.—SW

Dilemmas for Wheezing Peds

By Chris Miller, MD

Oymar K, Halvorsen T, Aksnes L. Mast cell activation and leukotriene secretion in wheezing infants. Relation to respiratory syncytial virus and outcome. Pediatr Allergy Immunol. 2006 Feb;17(1):37-42.

The wheezing infant is a common problem in pediatric medicine; however, the long-term outcome and risk for recurrent wheezing remains unclear. The authors of this study assert that the risk for recurrent wheezing may be related to the type of inflammation and specific underlying virus during the initial wheezing episode.

Several studies have evaluated the specific contribution of eosinophils to respiratory inflammation in the wheezing child. These studies have found that eosinophilic inflammation may play a role in the airway hyper-reactivity in a child with persistent wheezing. Conversely, little information is available regarding mast cell involvement. This prospective study was designed to assess mast cell activation, in relation to respiratory syncytial virus (RSV) infection and persistent wheezing in wheezing infants.

Researchers enrolled 106 wheezing infants who were subsequently admitted to the hospital. None of these infants had a prior history of wheezing. Infants with prior history of atopic disease, lung disease, or signs of bacterial infection were excluded. RSV testing of nasopharyngeal mucous was performed. Sixty-seven (63%) of the wheezing infants had RSV. An additional 23 healthy infants were selected as controls.

To assess the extent of mast cell activation, urinary prostaglandin F2 (U-PGF2) was measured. To assess for leukotriene secretion urinary leukotriene 4 (U-LTE4) was measured. To evaluate for persistence or reoccurrence of wheezing, a 20-month post-hospitalization follow-up was done. One hundred and three (97%) of the previously hospitalized wheezing infants were available for the follow-up.

The authors used the term “persistent wheezing” to describe those children who experienced at least three wheezing episodes including the first hospitalization. These recurrences were identified either by parental report utilizing a standardized questionnaire or physician/hospitalization records. The remaining children were considered “transient wheezers.”

Review of the data regarding U-PGF2, a specific marker for mast cell activation, showed U-PGF2 to be greatest in the RSV positive patients, followed by the RSV negative patients and finally by the control group. U-LTE4, and thus leukotriene involvement, was also found to be significantly elevated in both the RSV positive and negative wheezing infants compared with the controls. No significant difference was found in U-LTE4 between RSV-positive infants and RSV-negative infants. The transient wheezing infant had a higher U-PGF2 than the persistent wheezing infant. Transient wheezers also had a higher U-LTE4 compared with persistent wheezers, although this was not statistically significant.

With univariate regression analysis positive predictive factors for persistent wheezing included increasing age, RSV negative disease, parental atopy, and male gender. Negative predictive factors for persistent wheezing included an elevated U-PGF2 level.

In discussion the authors conclude that mast cell activation and leukotriene secretion is present in a wheezing infant as noted by increased U-PGF2 and U-LTE4 levels, respectively. Higher U-PGF2 levels in RSV-positive patients indicates that mast cell activation may play a bigger part in the inflammatory process of RSV-induced wheezing compared with non-RSV induced wheezing. Leukotrienes appear to be involved in both RSV and non-RSV wheezing infants. Despite these results, mast cell activation and leukotriene secretion do not appear to be associated with persistent wheezing.

Limitations of this interesting study include the small sample size, apparent lack of follow-up with the control patients, and the diagnosis of recurrent wheezing episodes being characterized by the parents.

Although there is a slight increase in injection site events with decreasing interval since a previous immunization, Tdap can be safely administered at intervals of greater than or equal to 18 months since a previous TD/Td vaccine.

Influenza Pneumonia in Pediatric Patients

Lahti E, Peltola V, Virkki R, et al. Influenza pneumonia. Pediatr Infect Dis J. 2006 Feb;25(2):160-164.

Influenza and pneumonia are common in children. The objective of this study was to describe the frequency and characteristics of laboratory-documented and radiographically proven influenza-associated pneumonia in children.

This retrospective, single site study was conducted at Turku University Hospital (Finland). Chart reviews of both inpatient and outpatient visits of children younger than 16 were performed for a 24-year period between 1980 through 2003. Children with influenza A or B antigen detected nasopharyngeal aspirates were identified. Also children with chest radiographs obtained during their influenza infection were identified. Clinical findings upon initial presentation were summarized, in addition to laboratory values for white blood cell count (WBC) and C-reactive protein (CRP).

A total of 936 patients with virologically confirmed influenza were identified. Of this total, 79% had influenza A and the remaining had influenza B. Chest radiographs were reported on 400 (43%) of these patients. Of the 400 films, 228 were initially read as having infiltrates. However, during over-reading of the films 70 chest radiographs did not have an infiltrate and an additional 24 films could not be found. In summary, 134 children had both confirmed influenza and radiographically proven pneumonia. Thus 14% of the children with influenza who also had a chest radiograph had pneumonia.

Clinical findings of the 134 patients with influenza and pneumonia were similar among those with influenza A or B. The most common symptoms were fever (98%), cough (84%), and rhinorrhea (65%). The classical findings of headaches and myalgias were difficult to uncover due to the young age of the patients (median age 2.2 years). Of the 134 identified patients with influenza and pneumonia only 27% presented with dyspnea and 22% with tachypnea. Crackles were heard in 22%, rhonchi in 43%, and decreased breath sounds in 10%. No abnormal auscultation findings were found in 32% of the children. Sixty-eight percent of the study population was admitted to the hospital. The rate of hospitalization was greater for the younger patients. One-third of the patients had received antibiotics prior to enrollment, and 80% of the children received antibiotics during the hospitalization or at time of discharge. Four children required ventilator therapy. One patient with muscular dystrophy died of severe pneumonia.

Laboratory assessment found that 89% of the children had WBC less than 15 x 109/liter. CRP values were normal or only slightly increased in 55% of the children. Three children (2%) had laboratory-documented concomitant bacterial infections. Of these three cases two were due to bacteremia and one to a positive tracheal aspirate. Five children (7%) had double viral infections.

In this hospital-based study 14% of the patients with influenza had radiographically proven pneumonia. The authors found that in contrast with what we know about adults with influenza pneumonia, data shows influenza pneumonia in children is generally a benign disease. The greater burden of disease tends to be in the children younger than three years of age. Respiratory clinical findings may be absent in light of radiographically proven pneumonia. Laboratory findings show that most children with influenza pneumonia have normal WBC counts and normal to only slightly elevated CRP levels.

Shortcomings of this informative study include the lack of direct evidence in proving that the presence of influenza in the upper respiratory tract is directly associated with the infiltrate of the lower respiratory tract. The data may also be skewed because fewer than one-half of the patients with influenza had chest radiographs. The authors’ conclusions demonstrated that clinical findings did not correlate well with radiographically proven infiltrates.—CM

Bradycardia During Methadone Therapy in an Infant

By Lisa Carney, MD

Wheeler AD, Tobias JD. Bradycardia during methadone therapy in an infant. Pediatr Crit Care Med. 2006;7(1):83-85.

This retrospective case report demonstrates the occurrence of bradycardia associated with the use of methadone administered to prevent withdrawal in an infant with physical tolerance following long-term opioid therapy in the PICU setting.

The authors describe the onset of sinus bradycardia in an infant following the initiation of methadone therapy as a transition for intravenous fentanyl administration. The onset of bradycardia was temporally related to standard doses of methadone. These episodes resolved with tactile stimulation. No other pathologic conditions were noted that could have been responsible for the bradycardia. Additionally, the episodes resolved with cessation of methadone therapy. It is unlikely that the bradycardia was merely a manifestation of deep sedation with methadone because the infant’s sedation scores were the same as when he had been receiving fentanyl, a time during which no bradycardia was noted.

When administering opioids, the clinician generally focuses on adverse effects such as respiratory depression, slowing of gastrointestinal motility, and physical dependence. But because methadone’s three-dimensional structure shares similarities with calcium channel antagonists, bradycardia may occur—especially at higher doses. This effect has been reported in the adult literature; however, this is the first report in an infant.

As pediatric hospitalists, we may receive a patient in transfer from the PICU who was recently started on methadone therapy. Given the relatively high frequency of this scenario, it is unclear why bradycardia has not been previously reported in the pediatric population. It may be that the effect was not attributed to methadone and in the majority of cases the slowing of the heart rate was likely to have been innocuous from a physiologic standpoint. What may be more significant is the unnecessary investigation into the etiology of the bradycardia if its relationship to methadone is not appreciated. However, there may be a subset of patients who will not tolerate the bradycardia. Thus, close monitoring is suggested during methadone therapy.

Kawasaki disease should be a diagnostic consideration in infants younger than six months with prolonged, unexplained febrile illnesses.

Innoculation Conundrums

Halperin SA, Sweet L, Baxendale D, et al. How soon after a prior tetanus-diphtheria vaccination can one give adult formulation tetanus-diphtheria-acellular pertussis vaccine? Pediatr Infect Dis J. 2006 Mar;25(3):195-200.

Adult tetanus/diphtheria toxoids and acellular pertussis vaccines (Tdap) have been developed to prevent pertussis in adolescents and adults. There are concerns that unacceptable rates of severe injection site reactions, including Arthus-type reactions might occur if Tdap is administered too soon after a previous tetanus/diphtheria toxoid vaccine, such as TD or Td.

This study was conducted via a school-based program where more than 7,000 children/adolescents in grades three-12 were enrolled. These students received Tdap vaccine at intervals from previous vaccination with TD or Td of either 18 months-nine years or greater than/equal to 10 years. The 18 month-nine year interval was further divided into eight cohorts. One cohort per year two to nine (+/- 0.5 years) since receipt of the last TD/Td. Approximately 85% of the students provided accurate documentation of adverse events. There were no serious/major adverse events. There were no differences in reports of fever. Injection site erythema and swelling were slightly and statistically significantly increased with those participants with the most recent prior TD/Td. The increase in these localized injection site events ranged from 3.75%-10.3%.

In summary, although there is a slight increase in injection site events with decreasing interval since a previous immunization, Tdap can be safely administered at intervals of greater than or equal to 18 months since a previous TD/Td vaccine.—LC

Viral Occurrences in Young Children

Wolf DG, Greenberg D, Kalkstein D, et al. Comparison of human metapneumovirus, respiratory syncytial virus and influenza A virus lower respiratory tract infections in hospitalized young children. Pediatr Infect Dis J. 2006;25(4):320-324.

The authors compared the clinical and demographic features of children with lower respiratory tract infection (LRI) caused by human metapneumovirus (HMPV), respiratory syncytial virus (RSV), and influenza A virus and sought to determine whether coinfection by HMPV and other respiratory viruses leads to increased disease severity.

This prospective study enrolled 516 children <5 years old who were admitted with LRI at the Soroka University Medical Center in Israel during a one-year period from November 2001 through October 2002. At least one virus was detected in 57% of the enrolled patients.

Of those 293 patients, the viral breakdown was as follows: HMPV (13%), RSV (20%), influenza A (15%), parainfluenza (7%), and adenovirus (2%). The seasonal distribution of HMPV infections resembled those of RSV and influenza with peak incidence between November and March. Twenty-four percent of the HMPV children had co-infections with other respiratory viruses, most commonly RSV.

HMPV patients were older than RSV patients (17.6 +/- 16.8 months versus 10.5 +/- 11.8 months). HMPV was associated with wheezing and hypoxemia at a rate similar to that of RSV and higher than that of influenza A. Atelectasis was more common among HMPV (40%) than among RSV and influenza patients (13%). HMPV was more often associated with a diagnosis of pneumonia than RSV and influenza. HMPV was also more often associated with a diagnosis of asthma and less often with a diagnosis of bronchiolitis than RSV, even when corrected for age. Children who had a co-infection with HMPV had a higher rate of gastrointestinal symptoms but did not show a more severe respiratory picture.

In conclusion, the clinical pattern of HMPV (wheezing, hypoxemia) more closely resembles that of RSV than that of influenza A LRI. Additionally, there was no difference in disease severity between children with HMPV and RSV infection. However, the differences in age, radiographic findings, and clinical diagnosis suggest that HMPV pathogenesis may differ from that of RSV.—LC

Kawasaki Disease in Infants Younger Than Six Months

By Judith Waldman, DO

Chang FY, Hwang B, Chen SJ, et al. Characteristics of Kawasaki disease in infants younger than six months of age. Pediatr Infect Dis J. 2006 Mar;25(3):241-244.

Pi-Chang Lee, MD, and colleagues compared the clinical manifestations, laboratory results, echocardiographic findings, treatment, and outcome between two groups of patients hospitalized with Kawasaki disease. Group one consisted of 20 patients younger than six months. Group two consisted of 100 patients older than six months. The data was collected by chart review.

Researchers found that the time from onset of disease to diagnosis was longer in infants younger than six months. Patients less than six months of age had a higher incidence of incomplete Kawasaki disease. A presentation of full diagnostic criteria within 10 days occurred more frequently in patients greater than six months of age. There was no significant difference in major clinical manifestations between the two groups. However, the frequency of gallbladder hydrops was higher in patients older than six months of age.

Group one had higher white blood cell counts, platelet counts, and triglyceride concentrations and lower hemoglobin values. Group one had higher incidence of coronary involvement, including irregular surface and/or perivascular brightness of coronary artery wall, coronary dilatation, and aneurysm formation. There was no significant difference in giant aneurysm formation between the two groups. Group one had a higher incidence of pericardial effusion and tricuspid regurgitation/mitral regurgitation. Fewer patients received IVIG within 10 days in the younger age group. Diagnostic delay and incomplete presentation postponed IVIG in the patients less than six months of age.

New recommendations pertaining to the diagnosis and treatment of Kawasaki disease in the American Academy of Pediatric’s Red Book in 2006 should be beneficial in making a more rapid diagnosis and thus more timely treatment. In the past, diagnosis of Kawasaki required five full days of fever. Now, IVIG can be started after four days of fever if the patient meets four out of the five total criteria for disease. In cases of incomplete Kawasaki disease, physicians should base diagnosis and treatment on laboratory test results instead of visible symptoms. Obtain a baseline echo as usual. The laboratory criteria are albumin 3 g/dL or less, anemia, high alanine amino transferase, platelets after 7 days to 450,000/mm3 or greater, WBC count is 15,000 mm3 or greater, and urine 10 WBC/high powered field or greater. For patients who do not respond to 2g/kg of IVIG, the new recommendation is to retreat these patients with another 2g/kg of IVIG or use pulse steroid therapy. Look for these recommendations in the new 2006 Red Book. TH

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