Nonoperative management of blunt liver and spleen injury in children: evaluation of the ATOMAC guideline using GRADE

BACKGROUND: Nonoperative management of liver and spleen injury should be achievable for more than 95% of children. Large national studies continue to show that some regions fail to meet these benchmarks. Simultaneously, current guidelines recommend hospitalization for injury grade + 2 (in days). A new treatment algorithm, the ATOMAC guideline, is in clinical use at many centers but has not been prospectively validated. METHODS: A literature review conducted through MEDLINE identified publications after the American Pediatric Surgery Association guidelines using the search terms blunt liver trauma pediatric, blunt spleen trauma pediatric, and blunt abdominal trauma pediatric. Decision points in the new algorithm generated clinical questions, and GRADE [Grading of Recommendations, Assessment, Development, and Evaluations] methodology was used to assess the evidence supporting the guideline. RESULTS: The algorithm generated 27 clinical questions. The algorithm was supported by six 1A recommendations, two 1B recommendations, one 2B recommendation, eight 2C recommendations, and ten 2D recommendations. The 1A recommendations included management based on hemodynamic status rather than grade of injury, support for an abbreviated period of bed rest, transfusion thresholds of 7.0 g/dL, exclusion of peritonitis from a guideline, accounting for local resources and concurrent injuries in the management of children failing to stabilize, as well as the use of a guideline in patients with multiple injuries. The use of more than 40 mL/kg or 4 U of blood to define end points for the guideline, and discharging stable patients before 24 hours received 1B recommendations. CONCLUSION: The original American Pediatric Surgery Association guideline for pediatric blunt solid organ injury was instrumental in improving care, but sufficient evidence now exists for an updated management guideline.(AU)

Laparoscopic repair of a right paraduodenal hernia in a child.

Paraduodenal hernias are infrequently occurring rotational anomalies. We report a case of a right paraduodenal hernia repaired via laparoscopy, which occurred in a 13-year-old boy.

Trypsin stimulates production of cytokines from peritoneal macrophages in vitro and in vivo.

Acute pancreatitis (AP) is characterized by release of proteolytic enzymes from the pancreas and a powerful inflammatory cytokine cascade that mediates the systemic manifestations and contributes to the mortality of the disease. The purpose of this study was to examine a potential link between pancreatic proteolytic enzymes, which are increased in AP, and cytokine production. To evaluate this, we incubated rat peritoneal macrophages (PMO) with increasing concentrations of trypsin and measured cytokine production. Supernatants from the cell cultures were assayed for TNF-alpha and IL-1beta, and the PMO were collected for the evaluation of cytokine mRNA by polymerase chain reaction (PCR). Further to evaluate the role of pancreatic proteases in triggering the cytokine cascade in AP, trypsin was injected into the peritoneal cavity of Sprague-Dawley rats, and the production of cytokines was measured in the peritoneal fluid. Controls included injection of inactivated trypsin. Incubation of PMO with trypsin in vitro resulted in a dose-dependent increase in TNF-alpha production with maximal response (2,660.5+/-748.8 pg/mL) at 10 microg/mL protease. Peak TNF-alpha and IL-1beta release was noted 16 h after stimulation of the PMO (2,759.5+/-698.0 pg/mL and 160,596+/-4,065 cpm, respectively). Trypsin-induced TNF-alpha production was not due to release of cell-associated cytokine, inasmuch as activation of PMO with this protease causing an increase in TNF-alpha mRNA by 30 minutes, reaching a 14-fold increase at 4 h. Trypsin-injected animals produced TNF-alpha-containing ascitic fluid in a dose-dependent manner with peak TNF-alpha at 2 h (371.3+/-180 pg/mL) versus control (53.8+/-11.2 pg/mL; p < 0.022). No TNF-alpha was found in ascites of rats injected with heat-inactivated trypsin. Histologic examination of trypsin-injected animals revealed evidence of pulmonary inflammation at 2 and 4 hours. We conclude that the proteolytic enzyme trypsin stimulates cytokine production from macrophages in vitro and in vivo. This model demonstrates for the first time that trypsin is a potential mediator of the cytokine response seen during AP.

Acute pancreatitis induces cytokine production in endotoxin-resistant mice.

OBJECTIVE: The purpose of this study was to determine whether pathologic progression and cytokine responses in acute pancreatitis (AP) are altered in the absence of endotoxemia. SUMMARY BACKGROUND DATA: Previous studies have demonstrated that AP is characterized by rapid production and release of inflammatory cytokines, which play a major role in the local pancreatic and systemic complications of this disease. Infection and endotoxemia have been implicated as a major source of morbidity and death in AP and as possible stimuli for the overwhelming cytokine response seen in this disease. METHODS: AP was induced by a choline-deficient and ethionine-supplemented diet for 4 days in normal C57BL/6J mice (controls, n = 23) and in CD14 knockout mice (CD14KO, n = 23), which cannot produce circulating cytokines in response to endotoxin. Control and endotoxin-resistant mice were killed at time 0, then at 24, 48, 72, and 96 hours after the start of the diet. At each time point serum was collected for amylase, glucose, and cytokine measurements (tumor necrosis factor-alpha [TNFalpha] and interleukin-1beta [IL1beta]), and the pancreas was removed for histologic examination. TNFalpha was measured with a bioassay using WEHI-2F cells and IL1beta with a bioassay using D10.G4.1 cells. RESULTS: CD14KO mice developed biochemical manifestations of AP with alterations in amylase levels, hypoglycemia, weight loss, and histologic changes of pancreatitis similar to the pattern seen in control mice. TNFalpha and IL1beta production had similar kinetics in both groups, with significant peak TNFalpha serum levels at 72 hours and a progressive rise of IL1beta levels throughout the study period. Histologic changes appeared earlier and were more pronounced in the control versus the CD14KO mice. However, the mortality rate was identical (20% at 96 hours) for both groups. CONCLUSIONS: These results demonstrate that the progression of AP, the cytokine response associated with the disease, and early death are independent of endotoxin action. These findings, which suggest that an uncharacterized stimulus is responsible for triggering the cytokine cascade in this disease, may have significant implications for the management of patients with AP.