Thomas Spentzas

Children With Respiratory Distress Treated With High-Flow Nasal Cannula

High-flow nasal cannula (HFNC) therapy is a treatment for respiratory distress in neonates and children. In the present study, we assessed its effectiveness, comfort, and possible mechanism of action. Methods: We reviewed records of 46 patients treated with HFNC and estimated the modified COMFORT score (7 to 35 units), the respiratory clinical scale (0 to 12 units), and the oxygen saturation level. Data were collected at time 0 (before the use of high-flow), time 2 (60 to 90 min post-application), and at time 3 (8 to 12 hours post-application). Furthermore, we measured the nasopharyngeal pressure while on continuous positive air pressure (CPAP) as well as the differences in ‘‘lung expansion’’ demonstrated by the prestudy and post-study chest x-ray. Results: There were significant improvements in the modified COMFORT score (F1,45 = 40.03, P < .05), respiratory clinical scale (F1.69,76.15 = 121.19, P < .05), and oxygen saturation (F2,90 = 101.54, P < .05). Application of HFNC therapy created a significant average positive expiratory pressure of 4.0 ± 1.99 (SE) cm H2O. X-rays taken after initiation of HFNC showed either improved aeration of the lungs or no changes in 40 of 46 patients. Mechanical ventilation was needed in 5 of 46 patients. Conclusion: Our study indicates that high-flow nasal cannula improves the respiratory scale score, the oxygen saturation, and the patient’s COMFORT scale. Its mechanism of action is application of mild positive airway pressure and lung volume recruitment.

Correlation of intraocular pressure with intracranial pressure in children with severe head injuries

Objective: To determine whether there was a correlation between tonometric measurements of the intraocular pressure and transducer measurements of the intracranial pressure in the acute setting, and whether intraocular pressure can be used as a surrogate measure of intracranial pressure. Children with traumatic brain injuries commonly develop increased intracranial pressure requiring surgical placement of a pressure transducer to measure the intracranial pressure during the acute recovery period. The increased intracranial pressure may cause engorgement of the orbital compartments via dilation of the episcleral veins and manifest as increased intraocular pressure. Design: Prospective study. Setting: Tertiary academic pediatric intensive care unit. Patients: Children admitted with severe traumatic brain injury. Interventions: Tonometric intraocular pressure measurements. Measurements and Main Results: We performed an Institutional Review Board-approved, prospective study on 36 children (age range, 2.9–15.1 yrs) with traumatic brain injuries, requiring intracranial pressure monitoring. A total of 274 intraocular pressure measurements were made after placement of the pressure transducer, and concordance between the sites of injury and measurement was documented. The average age of the patients was 8.3 yrs. The mean intraocular pressure, intracranial pressure difference was −0.5 ± 0.68 cm H2O, and the variance was 29.88 (sd, 5.47). The 95% confidence interval was between −11.22 and 10.22. With concordance between the sites of measurement and injury, the mean IOP, intracranial pressure difference was −0.02 ± 0.61 cm H2O (variance, 23.28; sd, 4.82; 95% confidence interval, − 9.47 to 9.42). Concordance reduced the variance of the intraocular pressure, intracranial pressure discrepancy by 20.3%. The Pearson intraocular pressure-intracranial pressure regression coefficient and the Krippendorffs &agr; reliability estimate analyses indicated good agreement. The patients age or Paco2 did not influence the intraocular pressure, intracranial pressure difference. Using 20 cm H2O as a normal intracranial pressure cutoff, the intraocular pressure had a specificity of 0.7 and sensitivity of 0.97; with concordance, the values improved to 0.78 and 0.96, respectively. Conclusions: Tonometry is a useful screening surrogate measure of intracranial pressure in children with traumatic brain injuries, but seems to lack the accuracy necessary for close management of intracranial pressure in the acute posttraumatic period.

Ketamine inhibits tumor necrosis factor secretion by RAW264.7 murine macrophages stimulated with antibiotic-exposed strains of community-associated, methicillin-resistant Staphylococcus aureus

BackgroundInfections caused by community-associated strains of methicillin-resistant Staphylococcus aureus (CA-MRSA) are associated with a marked and prolonged host inflammatory response. In a sepsis simulation model, we tested whether the anesthetic ketamine inhibits the macrophage TNF response to antibiotic-exposed CA-MRSA bacteria via its antagonism of N-methyl-D-aspartate (NMDA) receptors. RAW264.7 cells were stimulated for 18 hrs with 105 to 107 CFU/mL inocula of either of two prototypical CA-MRSA isolates, USA300 strain LAC and USA400 strain MW2, in the presence of either vancomycin or daptomycin. One hour before bacterial stimulation, ketamine was added with or without MK-801 (dizocilpine, a chemically unrelated non-competitive NMDA receptor antagonist), APV (D-2-amino-5-phosphono-valerate, a competitive NMDA receptor antagonist), NMDA, or combinations of these agents. Supernatants were collected and assayed for TNF concentration by ELISA.ResultsRAW264.7 cells exposed to either LAC or MW2 in the presence of daptomycin secreted less TNF than in the presence of vancomycin. The addition of ketamine inhibited macrophage TNF secretion after stimulation with either of the CA-MRSA isolates (LAC, MW2) in the presence of either antibiotic. The NMDA inhibitors, MK-801 and APV, also suppressed macrophage TNF secretion after stimulation with either of the antibiotic-exposed CA-MRSA isolates, and the effect was not additive or synergistic with ketamine. The addition of NMDA substrate augmented TNF secretion in response to the CA-MRSA bacteria, and the addition of APV suppressed the effect of NMDA in a dose-dependent fashion.ConclusionsKetamine inhibits TNF secretion by MRSA-stimulated RAW264.7 macrophages and the mechanism likely involves NMDA receptor antagonism. These findings may have therapeutic significance in MRSA sepsis.

Brain tumor resection in children: neurointensive care unit course and resource utilization.

Objective: To describe the pediatric intensive care unit (PICU) course and resource utilization for children with brain tumor resection and to identify factors predicting prolonged (>1 day) PICU length of stay. After craniotomy for brain tumor resection, children recover in the PICU. A few require critical care interventions and a >24-hr length of stay. Design: We reviewed all brain tumor resection patients admitted to the PICU over 2 yrs. Preoperative, intraoperative, and postoperative variables and tumor characteristics were examined. The extracted variables were compared between two groups with a length of stay in the PICU of >1 or <1 day. Setting: Pediatric intensive care unit in a tertiary academic childrens medical center. Patients: A total of 105 patients post brain tumor resection were admitted to the PICU over the study period and analyzed. Interventions: Record review. Measurements and Main Results: Thirty-two (31%) of 105 patients remained in the PICU for >1 day. The mean age of patients in the >1 day group was 5.0 ± 0.81 yrs and 8.78 ± 0.65 yrs in the <1 day group (p < .05). The estimated blood loss was 20 ± 2.37 mL/kg in the >1 day and 9 ± 0.92 mL/kg in the <1 day group (p < .05). Fifteen (14.3%) patients were mechanically ventilated on arrival in the PICU; these patients more often had a length of stay of >1 day (p < .05). The number of unexpected intensive care unit interventions were 0.7 per patient, were more common in the >1 day group, and included treatment of sodium abnormalities, new neurologic deficits, paresis, or seizures (p < .05). In a logistic regression model, estimated blood loss and intubation on arrival predicted longer lengths of stay in the PICU (odds ratio, 1.1; 95% confidence interval, 1.05−1.18; and odds ratio, 33; 95% confidence interval, 2.57−333, respectively), with a receiver operating characteristic curve of 0.86 and 95% confidence interval, 0.78−0.94. Conclusions: Large intraoperative estimated blood loss and intubation on arrival may be predictive of PICU lengths of stay of >1 day for children who have had a craniotomy for brain tumor resection. Intensive care unit interventions are more common in these children.

Role of bacterial components in macrophage activation by the LAC and MW2 strains of community-associated, methicillin-resistant Staphylococcus aureus

We tested the contribution of four staphylococcal components - PSM-α, PSM-β, δ-toxin, and PVL - in triggering macrophage secretion of tumor necrosis factor (TNF) and interleukins 6 (IL-6) and 12 (IL-12) by two prominent, circulating strains of community-associated, methicillin-resistant Staphylococcus aureus (CA-MRSA): LAC, USA300; MW2, USA400. RAW 264.7 murine macrophages were stimulated with live, antibiotic-exposed bacteria, and cytokine secretion was quantitated in supernatants. Deletion of PSM-α expression in LAC led to >50% reduction in macrophage TNF and IL-6 secretion and a 20% reduction in IL-12 secretion, while PSM-α deletion in MW2 did not significantly reduce macrophage TNF secretion but resulted in a 15-20% reduction in IL-6 and IL-12 secretion. Deletion of δ-toxin in either strain led to more than 50% reduction in macrophage IL-6 secretion and smaller reductions in macrophage TNF and IL-12 secretion (8-25%). Our data implicate both PSM-α and δ-toxin in stimulating macrophage cytokine responses to CA-MRSA bacteria.

Differential Role of Rapamycin and Torin/KU63794 in Inflammatory Response of 264.7 RAW Macrophages Stimulated by CA-MRSA

Background. Rapamycin suppresses the RAW264.7 macrophage mediated inflammatory response but in lower doses induces it. In the present study, we tested the suppression of the inflammatory response in the presence of mTOR 1 and 2 inhibitors, Torin and KU63794. Methods. RAW264.7 cells were stimulated for 18 hrs with 106 to 107 CFU/mL inocula of community-acquired- (CA-) MRSA isolate, USA400 strain MW2, in the presence of Vancomycin. Then, in sequential experiments, we added Torin, KU63794, and Rapamycin alone and in various combinations. Supernatants were collected and assayed for TNF, IL-1, IL-6, INF, and NO. Results. Rapamycin induces 10–20% of the inflammatory cascade at dose of 0.1 ng/mL and suppresses it by 60% at dose of 10 ng/mL. The induction is abolished in the presence of Torin KU63794. Torin and KU63794 are consistently suppressing cytokine production 50–60%. Conclusions. There is a differential response between Rapamycin (mTOR-1 inhibitor) and Torin KU63794 (mTOR 1 and 2 inhibitors). Torin and KU63794 exhibit a dose related suppression. Rapamycin exhibits a significant induction-suppression biphasic response. Knowledge of such response may allow manipulation of the septic inflammatory cascade for clinical advantages.

Pediatric Patients Seen in Port-au-Prince, Haiti

Port-au-Prince and southern Haiti were at the epicenter of a 7.0 magnitude earthquake on January 12, resulting in massive widespread destruction. About 3 million people were affected by the earthquake; the Haitian Government reported that 230 000 people had died, 300 000 were injured, and 1 000 000 made homeless, resulting from severe damage to 250 000 residences and 30 000 commercial buildings. Of the population of Haiti, 45% are in the pediatric age group and may constitute a higher proportion of those who were injured. In response to this disaster, Le Bonheur Children’s Hospital dispatched a surgical/trauma team to Port-auPrince, Haiti, on January 30. The team included 3 surgeons, 1 anesthesiologist, and 5 physicians, who were supported by a nurse anesthetist, surgical technician, emergency medical technician, and communications specialist. Medical supplies and equipment for treating earthquake victims with surgical interventions and medical conditions were sent, together with water, food, and other supplies for sustaining the team in Haiti. Humanitarian efforts were provided at a private hospital located in downtown Port-au-Prince. The hospital opened its doors for providing free care to all patients after the earthquake. We propose that the limited health care resources in Haiti must be mobilized and tailored to meet the health care needs of children.

Pulmonary Function in Infants with Swallowing Dysfunction

Background Swallowing dysfunction can lead to recurring aspiration and is frequently associated with chronic symptoms such as cough and wheezing in infants. Our objective was to describe the characteristics of infants with swallowing dysfunction, determine if pulmonary function abnormalities are detectable, and if they improve after therapy. Methods We studied 38 infants with a history of coughing and wheezing who had pulmonary function tests performed within two weeks of their diagnosis of swallowing dysfunction. The raised lung volume rapid thoracoabdominal compression technique was used. After 6 months of therapy, 17 of the infants repeated the tests. Results Initially, 25 had abnormal spirometry, 18 had abnormal plethysmography, and 15 demonstrated bronchodilator responsiveness. Six months later test were repeated for seventeen patients. Ten patients had continued abnormal spirometry, two patients remained normal, three patients’ abnormal spirometry had normalized, and two patients’ previously normal studies became abnormal. Eight of the 17 patients had continued abnormal plethysmography, six had continued normal plethysmography, and three patients’ normal plethysmography became abnormal. After 6 months of treatment, eight patients demonstrated bronchodilator responsiveness, of which five continued to demonstrate bronchodilator responsiveness and three developed responsiveness. The remainder either continued to be non- bronchodilator responsive (two) or lost responsiveness (three.) The findings of the abnormal tests in most infants tested is complicated by frequent occurrence of other co-morbidities in this population, including gastroesophageal reflux in 23 and passive smoke exposure in 13 of the infants. Conclusions The interpretation of lung function changes is complicated by the frequent association of swallowing dysfunction with gastroesophageal reflux and passive smoke exposure in this population. Six months of medical therapy for swallowing dysfunction/gastroesophageal reflux did not significantly improve pulmonary function in these infants. Long-term studies will be necessary to determine which of these changes persists into adulthood.

SNAP II Index An Alternative to the COMFORT Scale in Assessing the Level of Sedation in Mechanically Ventilated Pediatric Patients

Sedation monitoring is essential in pediatric patients on ventilatory support to achieve comfort and safety. The COMFORT scale was designed and validated to assess the level of sedation in intubated pediatric patients. However, it remains unreliable in pharmacologically paralyzed patients. The SNAP II index is calculated using an algorithm that incorporates high-frequency (80-420 Hz) electroencephalogram (EEG) components, known to be useful in discriminating between awake and unconscious states, unlike other measurements that only include low-frequency EEG segments such as the bispectral index score. Previous studies suggested that the SNAP II index is a reliable and sensitive indicator of the level of consciousness in adult patients. Despite its potential, no data are currently available in the pediatric critically ill population on ventilatory support. This is the first pilot study assessing the potential application of the SNAP II index in critically ill pediatric patients by comparing it to the commonly used COMFORT scale.

Rapamycin Augments the NMDA-Mediated TNF Suppression of MRSA-Stimulated RAW264.7 Murine Macrophages

Background. Methicillin-resistant Staphylococcus aureus (MRSA) can stimulate massive cytokine release. Ketamine suppresses tumor necrosis factor (TNF) secretion by MRSA-stimulated RAW264.7 macrophages, and the mechanism likely involves N-methyl-D-aspartic acid (NMDA) receptor antagonism. The downstream effects of NMDA-mediated TNF suppression, specifically the PI3K/Akt and mTOR modulation, have not been described. Methods. RAW264.7 cells were stimulated for 18 hrs with 105 to 107 CFU/mL inocula of either of two prototypical community-acquired- (CA-) MRSA isolates, USA300 strain LAC and USA400 strain MW2. Then we added the NMDA inhibitors ketamine or 2R-amino-5-phosphonopentanoate (AP5), NMDA substrate, LY294002, and rapamycin in various combinations. Results. NMDA inhibition suppressed TNF secretion by almost a third compared to the no-ketamine control. When NMDA substrate was added, the TNF secretion increased by 10%. Addition of LY294002 suppressed TNF production by macrophages by 20%. Rapamycin exhibited a concentration-dependent TNF induction-suppression response: induction at doses of 0.1 and 1 ng/mL and suppression at 10 and 100 ng/mL. Induction of TNF was abolished when LY294002 was added and the suppression became uniform. Ketamine-induced suppression of TNF secretion was intensified 10–15% when rapamycin was added, but not when LY294002 was added. Conclusion. These findings suggest that NMDA-induced TNF suppression can be augmented by concurrent mTOR inhibition.