Daniel P. Doody

Appendicitis in children: Current therapeutic recommendations

Wound infection is the most common source of morbidity in appendicitis. Most recent pediatric series use protocols of preoperative antibiotics with aerobic and anaerobic coverage, intraoperative lavage, no peritoneal or wound drains, and continuation of antibiotics postoperatively with complicated appendicitis. There still remains controversy concerning skin closure and the duration of antibiotic therapy. We report the results of a prospective protocol followed over 2 years with 420 children. The protocol was designed to determine whether the skin could be closed primarily in all patients undergoing appendectomy. Preoperatively all patients received triple antibiotics (ampicillin, gentamicin, and clindamycin) that were continued postoperatively for two doses if there was a normal appendix or simple acute appendicitis, for at least 3 days with gangrenous appendicitis, and at least 5 days with perforated appendicitis. Antibiotics were continued if the patient remained febrile or had a white count greater than 10,000. No drains were used and the skin was closed primarily. The overall infectious complication rate was 1.0% (4/420). Among those with a normal appendix or simple acute appendicitis there were no infectious complications. Among those with gangrenous or perforated appendicitis there were 1.7% wound infections (2/117) and 1.7% intraabdominal abscesses (2/117). Duration of hospitalization was 2.1 days (range, 1 to 5 days) after simple acute appendicitis and 6.9 days (range, 3 to 40 days) after gangrenous or perforated appendicitis. These results set new standards in terms of wound management, infectious complications, and length of hospital stay.

Prenatal glucocorticoid therapy reverses pulmonary immaturity in congenital diaphragmatic hernia in fetal sheep.

OBJECTIVE To assess the feasibility of conducting clinical trials of prenatal steroid therapy for congenital diaphragmatic hernia (CDH) in humans, the authors tested whether prenatal glucocorticoid, currently the standard treatment to minimize respiratory distress syndrome in premature infants, might improve the pulmonary immaturity in severe CDH in a large animal model. SUMMARY BACKGROUND DATA The authors have used the nitrofen-induced rat model of CDH, which demonstrates immature lungs by biochemical, morphometric, and molecular biologic criteria. They also have shown that the lethally immature lungs of the full-term CDH rats can be improved by biochemical, morphometric, physiologic, and molecular criteria by treating the mothers with parenteral steroids at doses extrapolated from the current therapy used to accelerate lung development of premature human babies. METHODS During a 3-year period in 88 fetal sheep, 1) left-sided diaphragmatic hernias were created surgically at varying gestational ages (day 78-90; term = 142-145 days) and size to maximize severity (n = 45), 2) placement and design of indwelling fetal intravenous catheters were optimized (n = 13), and 3) timing and dosage of cortisol administration were determined (n = 17). As a result, diaphragmatic hernias were created on day 80, intravenous catheters were placed on day 120, and twice-daily intravenous cortisol injections (n = 8) or saline as the control (n = 5) were administered (days 133-135). Lambs were delivered on day 136 via cesarean section to avoid steroid-induced abortion; vascular access was obtained, and the fetuses were ventilated at standard settings. Physiologic data were collected, and lungs were harvested for biochemical and histologic analysis. RESULTS Significant improvements were measured in postductal arterial oxygen pressure ([PaO2] 38 +/- 6 mmHg after cortisol therapy compared with 20 +/- 3 mmHg for saline controls; p = 0.002) and in dynamic compliance (0.42 +/- 0.05 mL/cm H2O vs. 0.29 +/- 0.01 mL/cm H2O; p = 0.01). Lung glycogen levels in the right lung of the cortisol group were significantly better than controls (4.6 +/- 0.3 mg/g lung vs. 6.8 +/- 0.4 mg/g; p = 0.002), as were protein/DNA levels (8.3 +/- 0.9 mg/mg vs. 14.5 +/- mg/mg; p < 0.05). Striking morphologic maturation of airway architecture was observed in the treated lungs. CONCLUSIONS Prenatal glucocorticoids correct the pulmonary immaturity of fetal sheep with CDH by physiologic, biochemical, and histologic criteria. These data, combined with previous small animal studies, have prompted the authors to initiate a prospective phase I/II clinical trial to examine the efficacy of prenatal glucocorticoids to improve the maturation of hypoplastic lungs associated with CDH.

Permissive Hypercapnia as a Ventilatory Strategy in Burned Children: Effect on Barotrauma, Pneumonia, and Mortality

OBJECTIVE To document the incidence of barotrauma, pneumonia, and respiratory death associated with a mechanical ventilation protocol based on permissive hypercapnia in pediatric burn patients. DESIGN Retrospective review. MATERIALS AND METHODS Patients were managed using a mechanical ventilation protocol based on permissive hypercapnia, tolerating moderate (pH > 7.20) respiratory acidosis to keep inflating pressures below 40 cm H2O. MAIN RESULTS Over a 2.5-year interval, 54 burned children (11% of 495 acute admissions) with an average age of 6.5 years (range 5 weeks to 17 years), average burn size of 44% (range 0 to 98%), and median burn size of 46% required mechanical ventilatory support for an average of 12.5 days (range 1 to 56 days). Inhalation injury was diagnosed in 34 (63%) of the children and 72% percent were admitted within 24 hours of injury. Overt barotrauma occurred in 5.6% of the patients, pneumonia in 32%, and respiratory death in 0%. CONCLUSIONS A conventional ventilation protocol based on permissive hypercapnia is associated with acceptable rates of barotrauma and pneumonia. The low incidence of respiratory death associated with this strategy suggests that it also minimizes ventilator-induced lung injury.

Left ventricular failure complicating severe pediatric burn injuries

PURPOSE Despite improvements in the overall survival rates for critically burned children, failed resuscitation may account for 54% of deaths following burn injuries. Clinical and experimental studies have implicated failure of the right side of the heart in adults, biventricular failure in elderly patients, and inadequate resuscitation as causes of refractory burn shock. This retrospective study of resuscitation at a tertiary pediatric burn center showed that myocardial depression is a complicating factor in the treatment of the pediatric burn victim. METHODS From 1989 to 1992, 28 critically burned children (> or = 60% total burn surface area) were resuscitated primarily at our center (admission within 24 hours of injury). Twenty-seven children had central lines, nine of whom underwent pulmonary artery catheterization for intensive hemodynamic monitoring because standard resuscitative therapy had failed. The average amount of fluid received at 8 and 24 hours after injury was within 10% of the calculated volume based on the Parkland formula. RESULTS Indexes of a failing rescue attempt included respiratory distress (PaO2/FlO2 < or = 200), central venous pressure of greater than 10 mm Hg, and urine output of less than 1 mL/kg/h. Filling pressures were found to be normal or elevated in all children, indicating adequate volume replacement. Evaluation of cardiac function was performed using a thermodilution technique and showed that 100% of the study group had depressed left ventricular function, with an average left ventricular stroke work index (LVSWI) of 19.9 g.m/m2 (normal, 44 to 68 g.m/m2), whereas only 38% had concomitant right ventricular failure. This left-sided dysfunction persisted throughout the acute resuscitation period but was improved after appropriate modification of fluid resuscitation and initiation of vasopressors (average final LVSWI, 38.0 g.m/m2). There were no complications from placement of the Swan-Ganz catheters in this group. CONCLUSION Cardiogenic failure is a major determinant of a failing pediatric burn resuscitation, and, contrary to the adult burn patient, the myocardial depression is predominantly left-sided. Information from pulmonary artery catheters can help direct therapy by providing indications for vasopressors and modifying fluid resuscitation.

The use of white blood cell count and left shift in the diagnosis of appendicitis in children.

Background: The use of white blood cell (WBC) count and left shift in the diagnosis of appendicitis in pediatric patients is unproven. It is commonly thought that children with appendicitis have an elevated WBC count with a left shift; however, most data supporting this belief stem from studies conducted on appendicitis in adults, not children. The purpose of this investigation was to determine the value of WBC count and differential in the diagnosis of appendicitis in children presenting to the emergency department (ED) with acute abdominal pain. Methods: Seven hundred twenty-two pediatric ED patients with a primary complaint of nontraumatic abdominal pain were identified by prospective and retrospective methods. White blood cell count with differential was performed on patients with history and physical examination findings that were felt to warrant laboratory investigation. Results of WBC counts were determined as low, normal, or high, with or without a left shift, based on normal age-related values per laboratory protocol for pediatric patients. Results: The diagnosis of appendicitis was made in 10.2% of all patients presenting to the ED with acute abdominal pain. Thirty percent of toddlers (1-3.9 years) with high WBC counts had appendicitis, whereas 0% of toddlers with low WBC counts and 4.8% of toddlers with normal WBC counts had appendicitis (χ2 = 6.5, P = 0.04). A normal WBC count did not rule out appendicitis in toddlers; however, the negative predictive value (NPV) for normal or low WBC count was high (NPV = 95.6%). In the child age group (4-11.9 years), high WBC count was both sensitive and specific for the diagnosis of appendicitis in children (sensitivity = 71%, specificity = 72%), and the NPV for normal or low WBC count was high (NPV = 89.5%). Lastly, 43.9% of adolescents (12-19 years) with high WBC counts had appendicitis, whereas 0% of adolescents with low WBC counts and 8.3% of adolescents with normal WBC counts had appendicitis (χ2 = 37.3, P < 0.001). The NPV for a low or normal WBC count was also high in the adolescent group (NPV = 91.9%). Left shift was also strongly associated with appendicitis. Among toddlers, 40% of patients with a left shift had appendicitis, whereas 1.8% of toddlers without a left shift had appendicitis (χ2 = 25.7, P < 0.001, NPV = 98.2%). Similarly, left shift was strongly associated with appendicitis in children and adolescents. Among children, 54.3% of patients with a left shift had appendicitis, whereas 5.4% of children without a left shift had appendicitis (χ2 = 67.8, P < 0.001, NPV = 90.5%). Among adolescents, 53.5% of patients with a left shift had appendicitis, whereas 6.1% of adolescents without a left shift had appendicitis (χ2 = 72.3, P < 0.001, NPV = 93.9%). In patients with a left shift, 51.2% had appendicitis, whereas 3.7% of patients without a left shift had appendicitis (χ2 = 226.2; P < 0.001, NPV = 96.3%). In all patients with appendicitis, elevated WBC counts had a sensitivity of 67% and a specificity of 80%. Using left shift alone as an indicator for appendicitis was associated with a sensitivity of 59% and a specificity of 90%. However, when a high WBC count and left shift were combined, the sensitivity climbed to 80%, and specificity remained at 79%. The sensitivity fell to 47% when both a high WBC count and left shift were analyzed, and specificity climbed to 94%. The positive likelihood ratio for a high WBC count and left shift was 9.8. Conclusions: The determination of WBC count and differential is useful in the diagnosis of appendicitis in children presenting to the ED with nontraumatic acute abdominal pain, regardless of age. High WBC counts and left shift are independently, strongly associated with appendicitis in children aged 1 to 19 years. In fact, for this subset of patients older than 4 years, the most common diagnosis in the setting of an elevated WBC count was appendicitis. The presence of an increased WBC count or left shift carries with it a high sensitivity (79%), and the presence of both high WBC count and left shift has the highest specificity (94%). These values are, therefore, helpful in the diagnosis and exclusion of appendicitis. Although not absolute, the WBC count and left shift can be helpful in the diagnosis and exclusion of appendicitis.

Extracorporeal Membrane Oxygenation for Nonneonatal Acute Respiratory Failure: The Massachusetts General Hospital Experience From 1990 to 2008

OBJECTIVE To determine the efficacy of extracorporeal membrane oxygenation (ECMO) for nonneonatal acute respiratory failure. DESIGN Single-institution, retrospective medical record review from February 1990 to March 2008. SETTING Tertiary care hospital. PATIENTS Eighty-one nonneonatal patients (mean age, 23 years; age range, 2 months to 61 years) with acute respiratory failure who had failed maximal ventilator support received ECMO therapy between 1990 and 2008. Patients were grouped into 6 categories based on diagnosis: sepsis (n = 8), bacterial or fungal pneumonia (n = 15), viral pneumonia (n = 9), trauma or burn (n = 10), immunocompromise (n = 15), and other (n = 24). Main Outcome Measure Survival to hospital discharge. RESULTS Overall survival was 53%. Survival was highest in patients with viral pneumonia (78%), followed by bacterial pneumonia (53%), sepsis syndrome (44%), and immunocompromise (40%). Patients treated following trauma or burns had the lowest survival (33%). The average age was 19 years for survivors as compared with 27 years for nonsurvivors. Survival was lower in patients with multiple organ failure as compared with those with single organ failure (33% vs 60%, respectively), in patients who experienced mechanical ventilation for longer than 10 days prior to the initiation of ECMO as compared with those who received ventilatory support for less than 10 days prior to the initiation of ECMO (31% vs 57%, respectively), and in patients requiring more than 400 hours of ECMO support as compared with those requiring less than 400 hours of ECMO support (42% vs 55%, respectively). CONCLUSIONS Therapy with ECMO may provide a survival benefit in carefully selected patients with nonneonatal acute respiratory failure who have failed maximal ventilator support. Nonneonatal survival with ECMO therapy is strongly dependent on diagnosis, with the highest survival seen in those with viral or bacterial pneumonia. Older age, multiple organ failure, prolonged ventilation prior to ECMO initiation, and long ECMO runs are associated with decreased survival.

Laryngotracheoesophageal cleft (type IV): Management and repair of lesions beyond the carina☆

Since the first successful repair of a complete laryngotracheoesophageal cleft (LTEC) to the carina in 1982, three newborn infants were observed with a particularly difficult variant in which the cleft extends beyond the carina into the mainstem bronchi. This type IV LTEC creates a long common tracheoesophagus, whose successful separation requires meticulous preoperative, operative, and postsurgical care. Three infants had complete surgical repair at our institution at 29, 49, and 225 days old and survived a minimum of 8 months. Recurrent tracheoesophageal fistulae at the thoracic inlet occurred in two infants, but was not observed in one patient when sternocleidomastoid muscle was interposed between the trachea and esophagus in the neck. Microgastria is an associated finding in each infant with the tracheoesophageal cleft extending beyond the carina. The small stomach is problematic as it is anatomically inadequate for any antireflux procedure and has not grown well, even with prolonged feeding. Early cleft repair is essential to prevent the development of chronic lung disease secondary to recurrent aspiration. The techniques to make the diagnosis, the preferred treatment to initially protect the airway, a single-stage operation performed simultaneously through the chest and neck to definitively repair the cleft, and finally the intraoperative and postoperative management critical for an optimal outcome are described.

Prenatal glucocorticoids improve pulmonary morphometrics in fetal sheep with congenital diaphragmatic hernia

PURPOSE Prenatal glucocorticoids reverse pulmonary immaturity in rodents with pharmacologically induced congenital diaphragmatic hernia (CDH). The authors applied quantitative stereologic morphometric techniques to test whether these effects could be reproduced in large animals (sheep) with surgically created CDH. METHODS Diaphragmatic hernias were created surgically in fetal lambs at gestational day 80. The fetuses were treated with intravenous cortisol (n = 6) or normal saline control (n = 5) from days 133 to 135. Lungs distended at 15 cm pressure from each group were harvested at day 136, processed histologically, and studied by brightfield microscopy at 400 x using a 42-point equidistant counting grid. Ten morphometric parameters (Mean +/- SEM) were measured by point-counting 60 fields/lung, and analysis of variance was performed. RESULTS The CDH-cortisol-treated lungs showed striking significant maturational improvements when compared with lungs of CDH-normal saline controls by seven of ten morphometric parameters. CONCLUSIONS (1) Prenatal glucocorticoids accelerate lung maturity in fetal lambs with CDH by seven quantitative morphometric parameters. (2) The observation that prenatal glucocorticoid therapy improves measures of maturity for both CDH rodent and sheep models encourages proceeding with a Phase I human clinical trial in ultrasound-confirmed CDH.

Antegrade colonic enemas and intestinal diversion are highly effective in the management of children with intractable constipation

PURPOSE Intractable constipation in children is an uncommon but debilitating condition. When medical therapy fails, surgery is warranted; but the optimal surgical approach has not been clearly defined. We reviewed our experience with operative management of intractable constipation to identify predictors of success and to compare outcomes after 3 surgical approaches: antegrade continence enema (ACE), enteral diversion, and primary resection. METHODS A retrospective review of pediatric patients undergoing ACE, diversion, or resection for intractable, idiopathic constipation from 1994 to 2007 was performed. Satisfactory outcome was defined as minimal fecal soiling and passage of stool at least every other day (ACE, resection) or functional enterostomy without abdominal distension (diversion). RESULTS Forty-four patients (range = 1-26 years, mean = 9 years) were included. Sixteen patients underwent ACE, 19 underwent primary diversion (5 ileostomy, 14 colostomy), and 9 had primary colonic resections. Satisfactory outcomes were achieved in 63%, 95%, and 22%, respectively. Of the 19 patients diverted, 14 had intestinal continuity reestablished at a mean of 27 months postdiversion, with all of these having a satisfactory outcome at an average follow-up of 56 months. Five patients underwent closure of the enterostomy without resection, whereas the remainder underwent resection of dysmotile colon based on preoperative colonic manometry studies. Of those undergoing ACE procedures, age younger than 12 years was a predictor of success, whereas preoperative colonic manometry was not predictive of outcome. Second manometry 1 year post-ACE showed improvement in all patients tested. On retrospective review, patient noncompliance contributed to ACE failure. CONCLUSIONS Antegrade continence enema and enteral diversion are very effective initial procedures in the management of intractable constipation. Greater than 90% of diverted patients have an excellent outcome after the eventual restoration of intestinal continuity. Colon resection should not be offered as initial therapy, as it is associated with nearly 80% failure rate and the frequent need for additional surgery.

Emergency intraosseous infusion in severely burned children

Severely burned patients require rapid administration of large volumes of isotonic fluids. Obtaining adequate intravenous (IV) access in children with greater than 70% total body surface area burns may be difficult, time-consuming, and sometimes impossible. This report describes the use of intraosseous infusion technique as a life-saving means of establishing IV access in two severely burned children.