Madelyn Kahana

Glutamine administration reduces Gram-negative bacteremia in severely burned patients: a prospective, randomized, double-blind trial versus isonitrogenous control.

Objective To determine the effect of intravenous glutamine supplementation vs. an isonitrogenous control on infectious morbidity in severely burned patients. Previous clinical studies in seriously ill patients suggest a beneficial effect of glutamine on infectious morbidity, but no trials have examined possible clinical benefits in severely burned patients. Design Prospective, double-blind, randomized trial. Setting Burn intensive care unit of a university hospital. Patients Twenty-six severe burn patients with total burn surface area of 25% to 90% and presence of full-thickness burns. Patients were evaluated for occurrence of bacteremia and antibiotic use during the first 30 days of their burn unit admission. Nutritional status and overall inflammation were also measured. Intervention Either intravenous glutamine or an isonitrogenous control amino acid solution was administered as a continuous infusion during burn intensive care unit stay. Measurements and Main Results The incidence of Gram-negative bacteremia was significantly reduced in the glutamine-supplemented group (8%) vs. control (43%;p < .04). No difference was seen in the incidence of Gram-positive bacteremia or fungemia. Average number of positive blood cultures, antibiotic usage, and mortality rates also were reduced but did not reach statistical significance. Significant improvements in serum transferrin and prealbumin were observed in glutamine-supplemented patients at 14 days after burn injury (p < .01 and .04, respectively). C-reactive protein was also significantly reduced at 14 days after burn injury in the glutamine group (p < .01). Conclusions Significantly fewer bacteremic episodes with Gram-negative organisms occurred in the glutamine-supplemented patients. Glutamine supplementation improved measures of nutrition and decreased measures of overall inflammation. In addition, a trend toward lower mortality rate, decreased overall bacteremia incidence, and antibiotic usage in the glutamine group was observed. Glutamine’s beneficial effects may be a result of improved gut integrity or immune function, but the precise mechanism of glutamine’s protection is unknown.

Glutamine reduces cytokine release, organ damage, and mortality in a rat model of endotoxemia

Clinical trials have demonstrated that glutamine (GLN) supplementation can decrease infectious morbidity and improve survival in a number of settings of critical illness. The mechanism of this protection remains unclear. The objective of this study was to evaluate the effect of GLN on cytokine release, organ injury, and survival from endotoxin-induced septic shock. Endotoxemia was induced in Male Sprague-Dawley rats by intravenous administration of 5 mg/kg Escherichia coli lipopolysaccharide (LPS). Concomitantly, animals were fluid resuscitated with a lactated ringers (LR) solution and given GLN (0.75 g/kg i.v.) or LR alone. Blood samples were obtained at multiple time points post-LPS injury for cytokine analysis. Survival rates were monitored for 72 h. Organ injury was evaluated in a separate set of animals via pathologic exam of tissues harvested 6 h post-LPS injury. A single dose of GLN significantly attenuated the release of TNF-alpha at 2 h (P < 0.005) and IL-1 beta at 4 h (P < 0.0001). This attenuation of cytokine release was associated with a significant decrease in mortality (P < 0.003). Pathologic exam demonstrated significant protection of both lung and small bowel tissue by GLN. Blood gas values 6-h post-LPS injury showed increased PaO2 and bicarbonate concentration in GLN treated animals. These data indicate that GLN can significantly attenuate pro-inflammatory cytokine release, protect against end-organ damage, and decrease mortality from endotoxemia. GLN confers protection even when administered at the onset of endotoxemia, rather then as pre-treatment. Thus, one explanation for the clinical benefits observed from GLN-supplementation may be related to the attenuation of pro-inflammatory cytokines.

Glutamine attenuates tumor necrosis factor-α release and enhances heat shock protein 72 in human peripheral blood mononuclear cells

OBJECTIVE Overexpression of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) can contribute to multiple organ dysfunction syndrome and septic shock in critically ill patients. We previously found that glutamine (GLN) can attenuate cytokine expression, induce heat shock protein 72 (HSP 72), and protect against endotoxin-induced mortality and organ injury in an in vivo rat model. However, data on the effect of GLN on direct attenuation of cytokine release and HSP 72 expression in human peripheral blood polymorphonuclear cells (PBMCs) is lacking. METHODS In this study, we assessed the effect of GLN on TNF-alpha and HSP 72 expression in human PBMCs. After treating with various doses of GLN, human PBMCs were stimulated with lipopolysaccharide (LPS). TNF-alpha release was analyzed via enzyme-linked immunosorbent assay and HSP 72 via western blot. RESULTS GLN at doses greater than 4 mM decreased TNF-alpha release at 4 and 24 h after LPS stimulation. Sublethal heating of PBMCs before LPS also markedly decreased TNF-alpha after LPS. Doses of GLN greater than 2 to 4 mM led to an increase in HSP 72 expression after LPS. CONCLUSION These results indicate that GLN, which may improve outcomes in critically ill patients, can directly attenuate pro-inflammatory cytokine release in PBMCs. This effect may be related to enhanced HSP 72 expression.

Catheter therapy of Swiss cheese ventricular septal defects using the Amplatzer muscular VSD occluder.

The medical and surgical management of patients with multiple muscular ventricular septal defects (VSDs) is associated with morbidity and mortality. Three children with Swiss cheese VSDs were treated with transcatheter occlusion of their multiple defects using the Amplatzer muscular VSD occluder. Seventeen defects were closed in five catheterization procedures. One patient had three devices placed in two procedures, the second had five defects closed in one procedure, and the third had nine defects closed in two procedures. Two patients had previously been treated with pulmonary artery banding and required subsequent surgical band removal. There was immediate reduction in the left‐to‐right shunting and clinical improvement in all patients. Complications included the need for blood transfusion during the two longest procedures and tricuspid valve regurgitation in one. Transcatheter occlusion of multiple VSDs is an acceptable alternative or adjunct to surgical therapy for these complex patients. Cathet Cardiovasc Intervent 2002;55:355–361.

The effect of premedication with OTFC, with or without ondansetron, on postoperative agitation, and nausea and vomiting in pediatric ambulatory patients.

Background : The purpose of this study was to evaluate, in the pediatric ambulatory surgical population, the efficacy of: (i) oral transmucosal fentanyl citrate (OTFC), when given preoperatively, to reduce postoperative excitement associated with sevoflurane, and (ii) intravenous ondansetron to reduce postoperative nausea and vomiting (PONV) associated with OTFC.

Decompressive hemicraniectomy in a 6-year-old male after unilateral hemispheric stroke: Case report and review

We report the case of a 6-year-old male who underwent a hemicraniectomy after a right-sided middle cerebral arterial infarct. This is the youngest patient reported to have undergone this procedure for stroke-associated brain swelling. This case illustrates that hemicraniectomy for stroke can be performed safely in pediatric patients, with potential brain- and lifesaving benefits.

Association between maintenance fluid tonicity and hospital-acquired hyponatremia.

OBJECTIVE To evaluate whether the administration of hypotonic fluids compared with isotonic fluids is associated with a greater risk for hyponatremia in hospitalized children. STUDY DESIGN Informatics-enabled cohort study of all hospitalizations at Lucile Packard Childrens Hospital between April 2009 and March 2011. Extraction and analysis of electronic medical record data identified normonatremic hospitalized children who received either hypotonic or isotonic intravenous maintenance fluids upon admission. The primary exposure was the administration of hypotonic maintenance fluids, and the primary outcome was the development of hyponatremia (serum sodium <135 mEq/L). RESULTS A total of 1048 normonatremic children received either hypotonic (n = 674) or isotonic (n = 374) maintenance fluids upon admission. Hyponatremia developed in 260 (38.6%) children who received hypotonic fluids and 104 (27.8%) of those who received isotonic fluids (unadjusted OR 1.63; 95% CI 1.24-2.15, P < .001). After we controlled for intergroup differences and potential confounders, patients receiving hypotonic fluids remained more likely to develop hyponatremia (aOR 1.37, 95% CI 1.03-1.84). Multivariable analysis identified additional factors associated with the development of hyponatremia, including surgical admission (aOR 1.44, 95% CI 1.09-1.91), cardiac admitting diagnosis (aOR 2.08, 95% CI 1.34-3.20), and hematology/oncology admitting diagnosis (aOR 2.37, 95% CI 1.74-3.25). CONCLUSIONS Hyponatremia was common regardless of maintenance fluid tonicity; however, the administration of hypotonic maintenance fluids compared with isotonic fluids was associated with a greater risk of developing hospital-acquired hyponatremia. Additional clinical characteristics modified the hyponatremic effect of hypotonic fluid, and it is possible that optimal maintenance fluid therapy now requires a more individualized approach.

The uncomfortable reality … We simply do not know if general anesthesia negatively impacts the neurocognitive development of our small children.

Annually in the United States more than one million children under the age of 5 years are exposed to anesthetics for therapeutic and diagnostic procedures. Pre-clinical data in animal models has consistently shown that anesthetic exposure to the developing brain results in long-term cognitive deficits. Current clinical data addressing the safety of these pharmaceutical agents on the developing human brain is limited. Recently, there has been an enormous amount of attention directed at this potential public health issue in both pre-clinical investigations and ongoing human research. A number of these studies should add to our understanding about the impact anesthetic exposure will have on the developing human brain. Until then, there is little data that absolutely reassures clinicians and parents that the pharmaceutical agents used are indeed safe for our children. The uncomfortable reality is that despite the fact that there are more than one million children younger than 5 years old who receive general anesthesia in the United States annually, and thousands more who are deeply sedated for imaging and diagnostic studies or as a necessary adjunct to care in the intensive care unit, there is little data that assures clinicians and parents that the pharmaceutical agents used are indeed safe for the developing brain. That said, there are no convincing human data to suggest that they are not.

Percutaneous closure of a giant coronary arteriovenous fistula using multiple devices in a 12-day-old neonate.

Coronary arteriovenous fistulas (CAVFs) are uncommon in children and are rarely reported in neonates. Larger fistulas usually require either surgical closure or percutaneous closure using a variety of different devices. Device closure of large fistulas in the immediate neonatal period has not been reported. We report the first case of a gigantic CAVF in a 12‐day‐old neonate (2.4 kg) where successful device closure was achieved in a staged approach using a 12 mm Amplatzer muscular VSD device, seven flipper coils, a 10/8 mm Amplatzer duct occluder device, as well as a 9 mm Gianturco Grifka vascular occlusion device. No complications were encountered and the patient was subsequently weaned off the ventilator. Catheter Cardiovasc Interv 2003;60:291–294.

Neuraxial Anesthesia in Parturients with Low Platelet Counts.

The obstetric anesthesiologist must consider the risk of spinal–epidural hematoma in patients with thrombocytopenia when choosing to provide neuraxial anesthesia. There are little data exploring this complication in the parturient. In this single-center retrospective study of 20,244 obstetric patients, the incidence of peripartum thrombocytopenia (platelet count <100,000/mm3) was 1.8% (368 patients). Of these patients, 69% (256) received neuraxial anesthesia. No neuraxial hematoma occurred in any of our patients. The upper 95% confidence limit for spinal–epidural hematoma in patients who received neuraxial anesthesia with a platelet count of <100,000/mm3 was 1.2%.