Frank A. Maffei

Hemodynamic Support in Fluid-refractory Pediatric Septic Shock

Objective. Assess outcome in children treated with inotrope, vasopressor, and/or vasodilator therapy for reversal of fluid-refractory and persistent septic shock. Design. Survey; case series. Setting. Three pediatric hospitals. Patients. Fifty consecutive patients with fluid-refractory septic shock with a pulmonary artery catheter within 6 hours of resuscitation. Interventions. Patients were categorized according to hemodynamic state and use of inotrope, vasopressor, and/or vasodilator therapy to maintain cardiac index (CI) >3.3 L/min/m2 and systemic vascular resistance >800 dyne-sec/cm 5 /m 2 to reverse shock. Outcome Measures. Hemodynamic state, response to class of cardiovascular therapy, and mortality. Results. After fluid resuscitation, 58% of the children had a low CI and responded to inotropic therapy with or without a vasodilator (group I), 20% had a high CI and low systemic vascular resistance and responded to vasopressor therapy alone (group II), and 22% had both vascular and cardiac dysfunction and responded to combined vasopressor and inotropic therapy (group III). Shock persisted in 36% of the children. Of the children in group I, 50% needed the addition of a vasodilator, and in group II, 50% of children needed the addition of an inotrope for evolving myocardial dysfunction. Four children showed a complete change in hemodynamic state and responded to a switch from inotrope to vasopressor therapy or vice versa. The overall 28-day survival rate was 80% (group I, 72%; group II, 90%; group III, 91%). Conclusions. Unlike adults, children with fluid-refractory shock are frequently hypodynamic and respond to inotrope and vasodilator therapy. Because hemodynamic states are heterogeneous and change with time, an incorrect cardiovascular therapeutic regimen should be suspected in any child with persistent shock. Outcome can be improved compared with historical literature.

Levels of Antimicrobial Molecules Defensin and Lactoferrin Are Elevated in the Cerebrospinal Fluid of Children With Meningitis

Objective: To measure levels of defensins and lactoferrin in the cerebrospinal fluid (CSF) of children with meningitis. Study Design. Prospective descriptive study involving children undergoing lumbar puncture during evaluation for meningitis. Methods. CSF concentrations of defensins and lactoferrin were determined using enzyme-linked immunosorbent assays on 19 children with bacterial meningitis, 31 children with aseptic meningitis, and 32 control children found to have normal CSF during evaluation for meningitis. Pertinent clinical and laboratory data were gathered on all children. Results. CSF concentrations of both defensins and lactoferrin were elevated markedly in children with bacterial and aseptic meningitis, compared with control children. No control subject had detectable levels of defensins in the CSF. Lactoferrin was undetectable in the CSF of 31 of 32 control subjects. Defensin and lactoferrin levels were significantly higher in the CSF of children with bacterial meningitis than in those with aseptic meningitis. Defensin levels in the CSF of children with bacterial meningitis ranged from 128 ng/mL to 99 430 ng/mL with a mean of 30 311 ng/mL (SD ± 28 865) and a median of 23 042 ng/mL. Defensin levels in the CSF of children with aseptic meningitis ranged from 0 ng/mL to 1675 ng/mL with a mean of 227 ng/mL (SD ± 433) and a median of 23 ng/mL. A significant correlation was found between defensin levels in the CSF and the total leukocyte count and the absolute neutrophil count in the CSF of children with bacterial meningitis. Lactoferrin levels in the CSF of children with bacterial meningitis ranged from 184 ng/mL to 31 412 ng/mL with a mean of 13 209 ng/mL (SD ± 9644) and a median of 10 382 ng/mL. Lactoferrin levels in the CSF of children with aseptic meningitis ranged from 0 ng/mL to 2715 ng/mL with a mean of 1042 ng/mL (SD ± 878) and a median of 852 ng/mL. No correlation was found between lactoferrin level in the CSF and the total leukocyte count or the absolute neutrophil count in the CSF of children with bacterial meningitis. In our study population, the sum total of CSF defensins and lactoferrin was found to be highly sensitive and specific in delineating bacterial from aseptic meningitis when compared with standard CSF studies. Conclusions. Significant elevations of defensins and lactoferrin, indicative of endogenous local antimicrobial peptide and polypeptide release, are found in the CSF of children with meningitis. We speculate that elevations in these antimicrobial molecules may reflect the intensity of the host response. Defensins seem to parallel neutrophil activation more closely than lactoferrin. Cumulative levels of CSF defensins and lactoferrin clearly distinguished bacterial meningitis from aseptic meningitis and control patients. Further investigation is warranted to determine the usefulness of measuring defensins and lactoferrin as a diagnostic tool and therapeutic monitor in the evaluation of children with meningitis.

Treatment of shigellosis with cefixime: two days vs. five days.

Background. Although the recommended standard course of therapy for shigellosis is 5 days of oral ampicillin or trimethoprim‐sulfamethoxazole therapy, successful outcome has been reported in adults treated with abbreviated courses of antibiotics. The purpose of this study was to compare short course (2‐day) vs. 5‐day therapy with cefixime for treatment of diarrheal disease caused by Shigella sonnei in children. Methods. This was a prospective, randomized, double blind, placebo‐controlled study. Patients were eligible if they were at least 6 months of age and presented to the Childrens Hospital of Pittsburgh during an outbreak of diarrhea caused by S. sonnei, with (1) a history of fever and diarrhea (at least three loose or watery stools per day), (2) bloody diarrhea or (3) diarrhea and known exposure to an individual with documented shigellosis. Patients were randomized to receive either 2 days of cefixime (8 mg/kg/day) given once daily followed by 3 days of placebo or 5 days of cefixime. Telephone follow‐up was performed on Days 3, 7 and 14 after enrollment. Follow‐up stool cultures were obtained on Day 7 to assess bacteriologic cure. There were standardized definitions for cure, improvement, failure and relapse. Results. Forty‐seven patients were enrolled. Eleven were eliminated from analysis because their stool cultures were not positive for S. sonnei. There were 36 evaluable patients, 21 in the 2‐day group and 15 in the 5‐day group. Patients ranged in age from 6 months to 17 years. Forty‐four percent of the subjects were male. Symptoms were improved or had resolved by Day 3 of therapy in all patients. There were 8 patients who experienced a clinical relapse: 5 of 21 (24%) patients in the 2‐day treatment group and 3 of 15 (20%) in the 5‐day group. There were 13 patients who experienced a bacteriologic failure (defined as the occurrence of a positive culture at the Day 7 follow‐up visit), 11 of 20 (55%) in the 2‐day group and 2 of 14 (14%) in the 5‐day group (P < 0.02). Conclusion. Two‐ and 5‐day treatment courses with cefixime for treatment of diarrheal disease caused by S. sonnei result in similar rates of clinical cure and clinical relapses; however, there was a higher rate of bacteriologic failure with shorter course therapy.

Duration of mechanical ventilation in life-threatening pediatric asthma: description of an acute asphyxial subgroup.

Objective. Acute asphyxial asthma (AAA) is well described in adult patients and is characterized by a sudden onset that may rapidly progress to a near-arrest state. Despite the initial severity of AAA, mechanical ventilation often restores gas exchange promptly, resulting in shorter durations of ventilation. We believe that AAA can occur in children and can lead to respiratory failure that requires mechanical ventilation. Furthermore, children with rapid-onset respiratory failure that requires intubation in the emergency department (ED) are more likely to have AAA and a shorter duration of mechanical ventilation than those intubated in the pediatric intensive care unit (PICU). Methods. An 11-year retrospective chart review (1991-2002) was conducted of all children who were aged 2 through 18 years and had the primary diagnosis of status asthmaticus and required mechanical ventilation. Results. During the study period, 33 (11.4%) of 290 PICU admissions for status asthmaticus required mechanical ventilation. Thirteen children presented with rapid respiratory failure en route, on arrival, or within 30 minutes of arrival to the ED versus 20 children who progressed to respiratory failure later in their ED course or in the PICU. Mean duration of mechanical ventilation was significantly shorter in the children who presented with rapid respiratory failure versus those with progressive respiratory failure (29 ± 43 hours vs 88 ± 72 hours). Children with rapid respiratory failure had greater improvements in ventilation and oxygenation than those with progressive respiratory failure as measured by pre- and postintubation changes in arterial carbon dioxide pressure, arterial oxygen pressure/fraction of inspired oxygen ratio, and alveolar-arterial gradient. According to site of intubation, 23 children required intubation in the ED, whereas 10 were intubated later in the PICU. Mean duration of mechanical ventilation was significantly shorter in the ED group versus the PICU group (42 ± 63 hours vs 118 ± 46 hours). There were significantly greater improvements in ventilation and oxygenation in the ED group versus the PICU group as measured by pre- and postintubation changes in arterial carbon dioxide pressure and arterial oxygen pressure/fraction of inspired oxygen ratio. Conclusions. AAA occurs in children and shares characteristics seen in adult counterparts. Need for early intubation is a marker for AAA and may not represent a failure to maximize preintubation therapies. AAA represents a distinct form of life-threatening asthma and requires additional study in children.

National survey of bedside ultrasound use in pediatric critical care

Objectives: The use of bedside ultrasound in critically ill adults has become standard practice. The current state of bedside ultrasound use in pediatric critical illness is unknown. The purpose of this study was to describe the use of bedside ultrasound in critically ill children with an emphasis on its use for establishing central vascular access. We also sought to describe current methods of training for bedside ultrasound use in pediatric critical care. Design: We conducted a cross-sectional survey on the use of bedside ultrasound in pediatric intensive care units in the United States. Measurements and Main Results: Pediatric critical care medical directors or their representatives from 128 of 230 eligible hospitals responded (56% response rate). The use of bedside ultrasound for vascular access was statistically more likely in units with >12 beds, >1,000 yearly admissions, and those with an active fellowship or pediatric cardiothoracic surgery program. Ultrasound was used at least once for vascular access in 82% (105 of 128) of responders, with 86% (90 of 105) using it on a regular basis. When using bedside ultrasound for vascular access, the preferred site is the internal jugular vein. A significant portion of responders use bedside ultrasound for nonvascular procedures such as assessing pleural or pericardial effusions. Despite the widespread use of bedside ultrasound, formal training is rare, occurring in only 20% (18 of 90) of current institutions that utilize bedside ultrasound. Conclusions: This national survey of the use of bedside ultrasound in pediatric critical care reveals widespread use of the technology. When using bedside ultrasound for vascular access, the preferred site is the internal jugular vein. Despite widespread use of bedside ultrasound, formal training that occurs routinely in other subspecialties is lacking. This survey provides meaningful demographic data that can be useful in planning future prospective studies and implementing formal training in bedside ultrasound for pediatric critical care fellows.

Resuscitation of a Pediatric Drowning in Hypothermic Cardiac Arrest

The prognosis of pediatric patients who require prolonged resuscitation after ice water drowning and hypothermic cardiac arrest remains guarded. We report a case of successful prolonged resuscitation of a pediatric patient in hypothermic cardiac arrest who showed severe metabolic derangements and went on to make a rapid and full neurologic recovery without the use of extracoproreal rewarming or mechanical cardiac support. Many ground and air medical emergency medical service programs have policies against interfacility transfer of patients in hypothermic cardiac arrest, calling into question the need to revise current protocols.

An unexpected finding on a pediatric chest radiograph

A 2-month-old male infant without significant perinatal history presented to the Emergency Department (ED) for evaluation of recurrent emesis. A barium swallow, obtained at 2 weeks of age after an apneic event, demonstrated gastroesophageal reflux. The child was started on ranitidine and cisapride, and he was changed to elemental formula. Despite these measures, the infant continued to have frequent post-prandial effortless emesis. A 1-day history of worsening emesis, rapid breathing, irritability, and post-tussive perioral cyanosis prompted the visit. His mother denied bilious or bloody emesis, fever, or diarrhea. Physical examination revealed a non-toxic, small, but vigorous infant. Initial vital signs included a temperature of 37.2°C, pulse 162 beats/min, respiratory rate 62 breaths/min, and blood pressure 80/58 mm Hg. His weight was 4 kg (tenth percentile for age). The respiratory examination revealed quiet tachypnea. The lung fields were clear to auscultation. Grunting, flaring, and retractions were absent. Oxyhemoglobin saturation obtained on room air was 99%. The remainder of the physical examination was normal. A chest X-ray study, obtained to look for evidence of pneumonia, revealed localized narrowing of the intrathoracic trachea best viewed on the lateral projection (Figure 1). The infant was admitted to the pediatric floor for further evaluation of the tracheal abnormality. Rigid bronchoscopy demonstrated significant compression of the right antero-lateral trachea by a pulsatile mass, consistent with an aberrant innominate artery. Rigid esophagoscopy showed hyperemia of the distal esophagus, and biopsy demonstrated grade II esophagitis, confirming the prior diagnosis of gastroesophageal reflux disease. Echocardiogram revealed no intracardiac lesion. Respiratory symptoms abated after surgical arteriopexy. He completed a course of antibiotics for presumed aspiration

Levels of Antimicrobial Molecules Defensin and Lactoferrin are elevated in the Cerebrospinal Fluid of Children with Bacterial Meningitis |[bull]| 384

Levels of Antimicrobial Molecules Defensin and Lactoferrin are elevated in the Cerebrospinal Fluid of Children with Bacterial Meningitis • 384

Treatment of Shigellosis with Cefixime: Two Days Vs Five Days. |[bull]| 740

BACKGROUND Although the recommended standard course of therapy for shigellosis is 5 days of oral ampicillin or trimethoprim-sulfamethoxazole therapy, successful outcome has been reported in adults treated with abbreviated courses of antibiotics. The purpose of this study was to compare short course (2-day) vs. 5-day therapy with cefixime for treatment of diarrheal disease caused by Shigella sonnei in children. METHODS This was a prospective, randomized, double blind, placebo-controlled study. Patients were eligible if they were at least 6 months of age and presented to the Childrens Hospital of Pittsburgh during an outbreak of diarrhea caused by S. sonnei, with (1) a history of fever and diarrhea (at least three loose or watery stools per day), (2) bloody diarrhea or (3) diarrhea and known exposure to an individual with documented shigellosis. Patients were randomized to receive either 2 days of cefixime (8 mg/kg(day) given once daily followed by 3 days of placebo or 5 days of cefixime. Telephone follow-up was performed on Days 3, 7 and 14 after enrollment. Follow-up stool cultures were obtained on Day 7 to assess bacteriologic cure. There were standardized definitions for cure, improvement, failure and relapse. RESULTS Forty-seven patients were enrolled. Eleven were eliminated from analysis because their stool cultures were not positive for S. sonnei. There were 36 evaluable patients, 21 in the 2-day group and 15 in the 5-day group. Patients ranged in age from 6 months to 17 years. Forty-four percent of the subjects were male. Symptoms were improved or had resolved by Day 3 of therapy in all patients. There were 8 patients who experienced a clinical relapse: 5 of 21 (24%) patients in the 2-day treatment group and 3 of 15 (20%) in the 5-day group. There were 13 patients who experienced a bacteriologic failure (defined as the occurrence of a positive culture at the Day 7 follow-up visit), 11 of 20 (55%) in the 2-day group and 2 of 14 (14%) in the 5-day group (P < 0.02). CONCLUSION Two- and 5-day treatment courses with cefixime for treatment of diarrheal disease caused by S. sonnei result in similar rates of clinical cure and clinical relapses; however, there was a higher rate of bacteriologic failure with shorter course therapy.