Rashed A. Hasan

Neuroleptic malignant syndrome associated with ziprasidone in an adolescent

BACKGROUND Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal disorder characterized by fever, muscular rigidity, delirium, and autonomic instability. Although the classic presentation of NMS has been most commonly associated with the typical neuroleptic medications, sporadic cases in association with atypical neuroleptic medications have been reported. OBJECTIVE We describe a case report of a pediatric patient with NMS associated with the use of the atypical antipsychotic medication ziprasidone hydrochloride. METHODS After a MEDLINE search of relevant literature (key terms: atypical antipsychotic, ziprasidone, neuroleptic malignant syndrome, and NMS; years: 1995-2004), no reports of NMS in association with ziprasidone in the pediatric population were identified. RESULTS The patient was a 15-year-old male adolescent with a history of schizoaffective disorder treated with ziprasidone capsules, 80 mg QD for 8 weeks prior to presentation. He was brought to the emergency department because the family noted that the child had a tactile fever; was rigid, diaphoretic, tremulous, and difficult to arouse; and had persistent urinary incontinence. The patient was admitted to the pediatric intensive care unit, where he remained rigid and unresponsive except for incoherent speech. He was treated for a presumptive diagnosis of NMS with IV dantrolene sodium (2 mg/kg q6h) to reduce the sequele of NMS; urinary alkalinization with sodium bicarbonate to maintain a urinary pH of 6.5 to 7.0; cardiac, pulse oximetry, and vital sign monitoring; and supportive care, including IV saline hydration. CONCLUSION We present this case to alert physicians of the possibility of NMS in adolescent patients treated with ziprasidone.

Cardiorespiratory Effects of Naloxone in Children

BACKGROUND: Data on the cardiorespiratory changes and complications following administration of naloxone in children are limited. OBJECTIVE: To evaluate the cardiorespiratory changes and complications following naloxone treatment in children. METHODS: The maximal changes in respiratory rate (RR), heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure, and any complications within 1 and 2 hours following naloxone were tabulated. RESULTS: One hundred ninety-five children received naloxone over 3 years. The mean ± SD age was 9.7 ± 6 years. The total doses of naloxone ranged from 0.01 to 7 mg (0.001–0.5 mg/kg body weight), with a median dose of 0.1 mg. Group 1 patients consisted of 11 6 (60%) children who were postoperative and had been given naloxone by an anesthesiologist; group 2 patients consisted of 79 (40%) children who received naloxone in the emergency department or pediatric intensive care unit. Patients in group 1 were older: 10.6 ± 5.3 versus 8.2 ± 6.7 years (p < 0.006), but received significantly lower doses of naloxone (0.09 ± 0.2 vs. 1.1 ± 0.76 mg; p < 0.001). When the entire cohort was evaluated, a significant increase in RR (15 ± 7 vs. 21 ± 8 breaths/min; p < 0.001), HR (102 ± 29 vs.107 ± 29 beats/min; p < 0.001), SBP (109 ± 17 vs. 115 ± 15 mm Hg; p < 0.001), and DBP (56 ± 10 vs. 60 ± 13 mm Hg; p < 0.001) within 1 hour following naloxone was noted. When the 2 groups were compared, only the changes in RR were greater in group 2 patients (6.8 ± 7.9 vs. 4.7 ± 5 breaths/min; p < 0.001) following naloxone. Systolic hypertension occurred in 33 of 195 (16.9%) of all patients, while diastolic hypertension occurred in 13 (6.6%) of all patients after naloxone. Only the incidence of diastolic hypertension was higher in group 2 compared with group 1 patients following naloxone (16% vs. 2%; p < 0.001). Hypertension resolved spontaneously. One child developed pulmonary edema and required positive pressure ventilation for 22 hours. CONCLUSIONS: Moderate increases in RR, HR, and BP occur after naloxone administration to children, but development of more serious complications is rare.

8-Isoprostane in the exhaled breath condensate of children hospitalized for status asthmaticus.

Objective: To evaluate the safety and feasibility of exhaled breath condensate (EBC) collection in children recovering from status asthmaticus (SA) in a pediatric intensive care unit (PICU); and to investigate whether 8-isoprostane (8-Iso) could be detected in the EBC of these children and to compare its concentration with that in the EBC collected from healthy children. Design: Prospective study. Setting: Multidisciplinary PICU in a teaching hospital. Patients: Sixteen consecutive patients (7–18 yrs of age) with SA and 16 age- and sex-matched controls. Interventions: The Wood clinical asthma score and the pulmonary index were used to assess the clinical severity of patients with SA upon admission to the PICU. EBC samples were collected within 24 hrs of admission to the PICU and were analyzed for the concentration of 8-Iso. Measurements and Main Results: Data are presented as mean ± sd values. There were no differences in age (12 ± 3.3 yrs vs.12 ± 2 yrs, p > .05) or sex (n = 10 males and n = 6 females in each group), between SA patients and controls. All patients with SA and the controls completed the EBC collection without complications. There was no statistically significant difference in the pulmonary index (3.2 ± 2.7 vs. 3.1 ± 2.8, p 0.9) post collection of EBC compared with the baseline values. There was a statistically significant correlation between Wood score and pulmonary index at the time of admission to the PICU in children with SA (r2 = .7, p < .01). The concentration of 8-Iso was significantly higher in the EBC of children with SA compared with controls (14.3 ± 1.8 pg/mL vs. 5.2 ± 0.7 pg/mL, p < .001). The correlation between the concentration 8-Iso and either the pulmonary index or Wood score at the time admission to the PICU was not statistically significant. Conclusions: EBC collection is well tolerated by children aged 7–18 yrs who are recovering from SA in a PICU. 8-Iso is elevated in the EBC from children with SA and may provide insight into the biochemical changes of oxidative stress in children in this clinical setting.

Kawasaki Disease Hospitalizations in a Predominantly African-American Population

This is a descriptive study of the occurrence of Kawasaki disease (KD) in an urban population that was a majority of African Americans. Records of 189 children (mean age, 2.9 ± 2.2 years [range: 2 months to 11.1 years]) hospitalized for KD over 8 years (January 1, 1992 to December 31, 1999) were reviewed and data analyzed. One hundred thirty-six (72%) were African American (AA), 43 (23%) were white, and 9 (5%) children were “others.” The annual frequency was 15 for AA and 7.7 for white per 100,000 5-year-old children. Coronary artery abnormalities (CAA) were reported in 21 (11%) children (18 [13.2%] of 136 AA, and 3 [4.7%] of 43 whites [p=0.095]). AA children with CAA were older than their white counterparts (26 to 24 vs. 5 to 2.8 months, p=0.03). There was a higher occurrence in winter and spring (110 cases [58%] vs. 79 cases [42%]) compared to summer and fall. KD occurrence was positively associated with average monthly snowfall (r=0.35, p=0.004) and inversely associated with average monthly temperature (r= - 0.2, p=0.048). African-American children were more likely to be hospitalized for KD compared to white children. The association of KD with temperature and precipitation suggest that it is influenced by environmental factors.

Group A Β-Hemolytic streptococcal bacteremia

Objective. The aim of this study was to review the clinical features, laboratory findings and the risk factors associated with invasive group A streptococcal infections in children admitted to our institution over a 9-year period (January 1, 1990 through December 31, 1999).Methods: Medical records of children who had a positive blood culture for group A betahemolytic streptococci and children who had this organism isolated from any other sterile site were identified and retrospectively reviewed.Results: Forty-one children with invasive GAS were identified, of whom 15 (36%) were diagnosed between 1990 and 1994, while the balance (26 patients, 63%) were diagnosed between 1995 and 1999 (p< 0.05). The mean age was 4.3 ± 2.5 years (age range: 2 months to 16 years). Thirteen (32%) patients were infants. Sixteen patients had only bacteremia, while 25 patients had in addition to bacteremia the following: cellulitis (n: 13), osteomyelitis (n: 6), pneumonia (n: 3), meningitis (n: 1), pharyngitis (n:3) and Toxic Shock Syndrome (n: 2). Primary varicella infection constituted the most common predisposing factor for invasive GAS infections and occurred in 11 (27%) patients. Leukocytosis (A white blood cell count > 15,000/ mm3) occurred in 21 (51 %) patients, while leukopenia (A white blood cell count < 5000/ mm3) occurred in 2 patients. Parenteral crystalline penicillin G followed by oral penicillin or amoxicillin were the most common antibiotics administered. The mean hospital length of stay was 8 days (range: 6–32 days). All, but one patient survived. The one patient who died had malnutrition and died from streptococcal toxic shock syndrome.Conclusion: More cases of invasive GAS were diagnosed during the second half of the study period, however, the overall rate of occurrence of bacteremia during the study period was consistent with previous reports. Primary varicella infection was the most common predisposing factor for invasive GAS infections. The low occurrence of toxic shock syndrome and fatalities among children with invasive GAS infections are consistent with other pediatric but not with adult series.

Invasive Aspergillosis in Children with Hematologic Malignancies

The respiratory tract is the most common system affected by aspergillosis in children with hematologic malignancies. However, Aspergillus spp. tend to invade blood vessels, resulting in systemic dissemination to multiple organs including, but not limited to, the brain, bones, liver, kidneys, and skin.Because early diagnosis and treatment are critical to the patient’s outcome, a high index of suspicion should be maintained in children with hematologic malignancies who are neutropenic and have prolonged fever that is unresponsive to systemic antibacterials. Several diagnostic modalities should be used simultaneously in order to establish the diagnosis in an expeditious manner. Detailed radiographic evaluations with plain radiographs, and CT scans of the chest, sinuses, brain, and other organs should be performed as soon as clinical suspicion is raised. Detection of circulating antigens, such as galactomannan and 1,3-β-glucan, and polymerase chain reaction appear promising in aiding in the diagnosis. A definitive diagnosis requires both a positive culture from a sterile site and evidence of tissue damage demonstrated by imaging studies or microscopic evaluations of sites of infection.Because the mortality rate is very high, empiric systemic antifungal therapy with amphotericin B, or one of its lipid formulations, should be initiated while laboratory investigations to substantiate or refute the diagnosis are continued. Surgical intervention is associated with a high mortality rate but may be of benefit in children with localized disease.

Oral dextromethorphan reduces perioperative analgesic administration in children undergoing tympanomastoid surgery.

OBJECTIVE: To determine whether oral dextromethorphan (1 mg/kg) given one hour prior to surgery decreases opioid administration in the perioperative period in children undergoing tympanomastoid surgery. METHODS: This was a prospective randomized double-blinded and placebo-controlled study in which 20 male and 18 female children (age 11.5 ± 3.5 years) were enrolled. Nineteen children received dextromethorphan (DM), while the other 19 received placebos. Postoperative pain was assessed using a visual analogue scale and a pain score of ≥5 was treated with intravenous morphine sulfate. Patients were discharged home on oral oxycodone. RESULTS: The total doses of fentanyl administered during surgery were higher in the placebo group compared to the DM group (4.1 ± 2 vs 2.6 ± 1.4 μg/kg, P = 0.02) and the total doses of intravenous morphine administered in the postoperative period were also higher in the placebo group compared to the DM group (150 ± 80 vs 73 ± 56 μg/kg, P = 0.004). The placebo group had a higher pain score at the time of admission to the Day Surgery Unit (DSU) and a higher maximum pain score, compared to the DM group, during their combined stay in the Post-Anesthesia Care Unit and DSU (7.3 ± 1.5 vs 3.1 ± 2.6, P = 0.001). CONCLUSIONS: Premedication with DM reduces the need for opioid administration in the perioperative period in children undergoing tympanomastoid surgery. EBM rating: A.

Treatment of invasive aspergillosis in children with hematologic malignancies

The respiratory tract is the most common organ involved with Aspergillosis in children with hematologic malignancies. AlsoAspergillus species tend to invade blood vessels resulting in systemic dissemination to multiple organs. Early diagnosis and treatment are pivotal to the patient’s outcome. A high index of suspicion should be maintained in children who have profound neutropenia and present with prolonged fever that is unresponsive to systemic antibiotics. Several diagnostic modalities should be used simultaneously in order to confirm the diagnosis in an expedited manner. Combination and sequential antifungal therapy have been shown to be of added benefit. Surgical intervention is associated with a high mortality rate, but may be indicated in children with a localized disease. In this article the authors review the epidemiology, microbiology, pathology, and clinical manifestations of invasive aspergillosis in children with hematologic malignancies. Current diagnostic approach, medical, and surgical treatment options are discussed.

Pulmonary Tuberculosis Outbreak in a Pediatric Population

Community-based outbreaks of Mycobacterium tuberculosis are uncommon in the United States but represent a dramatic type of epidemic that can lead to considerable investigations. Most of our knowledge regarding spread of tuberculosis (TB) has accumulated from the study of outbreaks. We describe the most recent outbreak of TB in Genesee County, Michigan. In February 2007, isoniazid-sensitive infectious pulmonary TB was identified in a 45-year-old African American grandmother who frequently provided care for her grandchildren and other children. The source case was reported to the Genesee County Health Department, which started an investigation to identify family and social contacts. We reviewed past medical records of contacts and prioritized them for evaluation based on the period of exposure to the index case. Health department staff screened contacts using clinical evaluation, tuberculin skin test, and chest radiography when indicated. Results were reviewed, and data were analyzed using descriptive inferential and epidemiological statistics.

Fulminant Hemorrhagic Pneumonitis

A7-day-old female infant was admitted to the pediatric intensive care unit (PICU) because of fever, rapid breathing, poor feeding, and lethargy. She was born by spontaneous vaginal delivery at 41 weeks of gestation to a 34-year-old mother after an uneventful pregnancy. There was no history of prolonged rupture of amniotic membranes or maternal fever during labor. There was no history of sexually transmitted diseases or of oral or genital lesions in the parents or siblings. The mother’s prenatal serologic tests for syphilis and group B beta-hemolytic streptococci were negative. On initial physical examination the infant was in moderate respiratory distress with intercostal retractions and a respiratory rate of 65 bpm, but the oxyhemoglobin saturation (SpO2) was 95% without oxygen supplementation. She was mildly dehydrated and lethargic. Temperature was 96.8°F and pulse 160/min. Blood pressure in the right upper and right lower extremities were 80/58 and 84/60 mm Hg, respectively. Upon auscultation of the chest bilateral f ine rales and rhonchi were noted. There were no cutaneous or mucous membrane lesions. The initial chest radiograph disclosed bilateral interstitial infiltrates with a normal cardiothoracic ratio. There was no evidence of pnenemothorax or pleural effusion. Initial laboratory studies revealed a white blood cell (WBC) count of 13,600/mm3 with 80% polymorphonuclear leucocytes, 6% band cells, 11% lymphocytes, 3% monocytes; hemoglobin, 14.5 g/dL, and hematocrit, 43%. The cerebrospinal fluid (CSF) showed 6 WBC/mm3, 9 red blood cells (RBC)/mm3, a protein level of 67 mg/dL, and a glucose level of 68 mg/dL. CSF Gram stain and tests for bacterial antigens, by latex agglutination particles, were negative. Serum transaminases and coagulation profile were within normal limits. Intravenous ampicillin sodium, 400 mg/kg/day, and cefotaxime, 200 mg/kg/day, were initiated. The infant’s respiratory status worsened with progressively increasing respiratory rate and hypoxemia. Arterial blood gases (on 100% oxygen) at this time showed the following values: pH, 7.3; partial pressure of carbon dioxide (PaCO2) 47 mm Hg; and partial pressure of arterial oxygen (PaO2) 45 mm Hg. Tracheal intubation and ventilatory support were necessary 8 hours after hospitalization. Following an atraumatic tracheal intubation, fresh blood and serosanguineous tracheal effluent were retrieved. The bloody tracheal effluent resolved following application of 10 cm H2O of positive end-expirator y pressure (PEEP). The repeat chest radiograph showed worsening of the bilateral interstitial infiltrates (Figure 1). The Gram stain of the pulmonary aspirates did not reveal any bacteria. The possibility of a viral etiology for the pneumonia was entertained and respiratory aspirates obtained via the endotracheal tube were submitted for viral cultures including the following: respiratory syncytial virus, parainfluenza, influenza, adenovirus, and HSV type 1 and 2. Oral swabs, urine, stool and CSF were submitted for herpes simplex virus (HSV) types 1 and 2