The optimum strategy for mechanical ventilation in a child with status asthmaticus is not established. Volume-controlled ventilation continues to be the traditional approach in such children. ...Pressure-controlled ventilation may be theoretically more advantageous in allowing for more uniform ventilation. We describe our experience with pressure-controlled ventilation in children with severe respiratory failure from status asthmaticus.
Retrospective review.
Pediatric intensive care unit in a university-affiliated children's hospital.
All patients who received mechanical ventilation for status asthmaticus.
Pressure-controlled ventilation was used as the initial ventilatory strategy. The optimum pressure control, rate, and inspiratory and expiratory time were determined based on blood gas values, flow waveform, and exhaled tidal volume.
Forty patients were admitted for 51 episodes of severe status asthmaticus requiring mechanical ventilation. Before the institution of pressure-controlled ventilation, median pH and Pco(2) were 7.21 (range, 6.65-7.39) and 65 torr (29-264 torr), respectively. Four hours after pressure-controlled ventilation, median pH increased to 7.31 (6.98-7.45, p <.005), and Pco(2) decreased to 41 torr (21-118 torr, p <.005). For patients with respiratory acidosis (Pco(2) >45 torr) within 1 hr of starting pressure-controlled ventilation, the median length of time until Pco(2) decreased to <45 torr was 5 hrs (1-51 hrs). Oxygen saturation was maintained >95% in all patients. Two patients had pneumomediastinum before pressure-controlled ventilation. One patient each developed pneumothorax and subcutaneous emphysema after initiation of pressure-controlled ventilation. All patients survived without any neurologic morbidity. Median duration of mechanical ventilation was 29 hrs (4-107 hrs), intensive care stay was 56 hrs (17-183 hrs), and hospitalization was 5 days (2-20 days).
Based on this retrospective study, we suggest that pressure-controlled ventilation is an effective ventilatory strategy in severe status asthmaticus in children. Pressure-controlled ventilation represents a therapeutic option in the management of such children.
The objective of this study is to determine if heat stress prior to endotoxemia diminishes cardiopulmonary dysfunction by attenuating the cytokine inflammatory response. Rats were assigned to either: ...1) neutropenia; 2) heat; 3) neutropenia, LPS; or 4) heat, neutropenia, LPS. Heart rate, blood gases, and blood, lung lavage, and lung mRNA for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and macrophage inflammatory protein (MIP)-2 were measured. Heat given before LPS resulted in a similar A-a O(2) gradient as the heat-alone and neutropenic groups (8 +/- 8 versus 8 +/- 7 versus 4 +/- 3 mm Hg) and a lower A-a O(2) gradient when compared to the neutropenic, LPS rats (8 +/- 8 versus 22 +/- 8 mm Hg, p < 0.003). Blood, lung lavage, and lung mRNA for TNF-alpha, IL-1beta, and MIP-2 were similar in the LPS rats regardless of heat. Heart rate was similar in both LPS groups but higher than non-LPS groups. Heat pretreatment attenuates lung injury in the neutropenic, endotoxemic rat but not by decreasing TNF-alpha, IL-1beta, or MIP-2 in the lung. Heat prior to LPS did not prevent cardiac dysfunction in neutropenic rats.
Limited data exist on the effects of extracorporeal membrane oxygenation on pharmacokinetics of cefepime in critically ill pediatric patients. The objective was to describe cefepime disposition in ...children treated with extracorporeal membrane oxygenation using population pharmacokinetic modeling.
Multicenter, prospective observational study.
The pediatric and cardiac ICUs of six sites of the Collaborative Pediatric Critical Care Research Network.
Seventeen critically ill children (30 d to < 2 yr old) on extracorporeal membrane oxygenation who received cefepime as standard of care between January 4, 2014, and August 24, 2015, were enrolled.
None.
A pharmacokinetic model was developed to evaluate cefepime disposition differences due to extracorporeal membrane oxygenation. A two-compartment model with linear elimination, weight effects on clearance, intercompartmental clearance (Q), central volume of distribution (V1), and peripheral volume of distribution (V2) adequately described the data. The typical value of clearance in this study was 7.1 mL/min (1.9 mL/min/kg) for a patient weighing 5.8 kg. This value decreased by approximately 40% with the addition of renal replacement therapy. The typical value for V1 was 1,170 mL. In the setting of blood transfusions, V1 increased by over two-fold but was reduced with increasing age of the extracorporeal membrane oxygenation circuit oxygenator.
Cefepime clearance was reduced in pediatric patients treated with extracorporeal membrane oxygenation compared with previously reported values in children not receiving extracorporeal membrane oxygenation. The model demonstrated that the age of the extracorporeal membrane oxygenation circuit oxygenator is inversely correlated to V1. For free cefepime, only 14 of the 19 doses (74%) demonstrated a fT_minimum inhibitory concentration of 16 mg/L, an appropriate target for the treatment of pseudomonal infections, for greater than 70% of the dosing interval. Pediatric patients on extracorporeal membrane oxygenation might benefit from the addition of therapeutic drug monitoring of cefepime to assure appropriate dosing.
To determine whether heat stress protects the endotoxemic rat by up-regulation of the counterinflammatory cytokine interleukin (IL)-10, thereby attenuating the inflammatory response.
A total of 16 ...rats were assigned to either the heat stress group (n = 8) or the control group (n = 8). The heat stress group was warmed to a temperature of >42 degrees C (107.6 degrees F) rectally for 10-15 mins; 20 hrs later, all rats were intubated, paralyzed, and ventilated. After jugular venous and arterial catheterization, endotoxin was given intravenously. Arterial blood was removed at 0, 2, 4, and 5 hrs for blood gases, tumor necrosis factor (TNF)-alpha, nitric oxide metabolites (NO), IL-10, and macrophage inflammatory protein (MIP)-2. The alveolar macrophages were removed, counted, and then incubated for 24 hrs. The supernatant was analyzed for TNF-alpha, NO, IL-10, and MIP-2.
University research laboratory.
Male Sprague-Dawley rats (n = 16).
Administration of heat before endotoxin infusion.
Alveolar-arterial oxygen gradient was lower in the heat stress group at 4 and 5 hrs after endotoxemia. Plasma and alveolar macrophage supernatant concentrations of TNF-alpha, NO, and IL-10 were not affected by heat. Plasma and alveolar macrophage supernatant MIP-2 concentrations were higher in endotoxemic rats receiving heat pretreatment compared with controls.
Our study demonstrates that heat leads to pulmonary protection of short duration in severe endotoxemia. This protection was not mediated by plasma TNF-alpha, IL-10, or NO. Contrary to our hypothesis, pretreatment with heat increased rather than decreased the plasma MIP-2 concentration and alveolar macrophage production of MIP-2 in endotoxemia. The mechanism of heat-conferred pulmonary protection in endotoxemia remains unclear. Alveolar macrophages do not produce IL-10 in endotoxemia. The increased MIP-2 production by heated alveolar macrophages was not attributable to alterations in production of either TNF-alpha or IL-10. The significance of increased MIP-2 by endotoxin-exposed alveolar macrophages in heated rats is unknown.
a) To demonstrate the effect of high-frequency ventilation on gas exchange in children with severe acute respiratory failure unresponsive to conventional ventilation; b) to identify patients at high ...risk of death early after institution of high-frequency ventilation.
Tertiary care pediatric intensive care unit in a university hospital.
A cross-sectional, observational study with factorial design.
Thirty-one patients with severe acute respiratory failure defined as a Pao2/F1o2 of < 150 torr (< 20 kPa) with a positive end-expiratory pressure of > or = 8 cm H2O and/or Paco2 of > 60 torr (> 8 kPa) with an arterial pH < 7.25.
Patients received either high-frequency oscillation or jet ventilation if respiratory failure was unresponsive to conventional ventilation and if the underlying disease process was deemed reversible.
Thirty-one children were managed with high-frequency ventilation, 11 children with jet and 20 children with oscillator. Arterial blood gases and level of ventilatory support were recorded before and at 6, 24, 48, 72, and 96 hrs after institution of high-frequency ventilation. There was an improvement in an arterial pH, Paco2, Pao2, and Pao2/FID2 6 hrs after institution of high-frequency ventilation (p < .01). This improvement, along with decreased need for oxygen, was sustained through the subsequent course. Twenty-three (74%) of 31 children treated with high-frequency ventilation survived. Survivors showed an increase in an arterial pH, Pao2, Pao2/FIO2, and a decrease in Paco2 within 6 hrs, whereas nonsurvivors did not. Oxygenation index was the best predictor of outcome. A combination of an initial oxygenation index of > 20 and failure to decrease the oxygenation index by > 20% by 6 hrs after initiation of high-frequency ventilation predicted death with 88% (7/8) sensitivity and 83% (19/23) specificity, with an odds ratio of 33 (p = .0036, 95% confidence interval 3-365).
In patients with potentially reversible underlying diseases resulting in severe acute respiratory failure that is unresponsive to conventional ventilation, high-frequency ventilation improves gas exchange in a rapid and sustained fashion. The magnitude of impaired oxygenation and its improvement after high-frequency ventilation can predict outcome within 6 hrs.
Elevated plasma lactate has been shown to correlate with mortality in patients with septic shock. Heat stress prior to sepsis has resulted in reduction in acute lung injury and mortality. We ...investigated whether heat stress resulted in decreased plasma lactate concentration and protected the lung by decreasing the inflammatory response to sepsis.
Plasma lactate concentration was elevated in septic rats without prior heat stress. Lactic acid levels were significantly lower in heat-treated septic rats (P < 0.05) and were not significantly different when compared with control rats. Septic rats with or without heat pretreatment had significantly higher myeloperoxidase activity in the lung than did control groups. Heat pretreatment did not prevent neutrophil infiltration or inflammatory mediator production in the lung.
Prior heat stress ameliorates lactic acidemia in rat sepsis. Heat stress did not attenuate the pulmonary inflammatory process. The mechanism of heat-induced protection from lactic acidemia in sepsis needs to be further explored.
To determine the diagnostic value of cerebrospinal fluid tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6 released into the cerebrospinal fluid of patients with ...ventriculoperitoneal shunt infection.
Prospective, observational study.
University teaching hospital.
Sixty-four patients requiring cerebrospinal fluid aspiration for suspected ventriculoperitoneal shunt malfunction.
Cerebrospinal fluid samples were obtained by shunt aspiration at the time of patient presentation.
TNF-alpha and IL-1 beta concentrations were measured by enzyme-linked immunosorbent assay, and IL-6 activity by bioassay. The sensitivity, specificity, predictive values, and overall efficiency for each cytokine were determined based on the cerebrospinal fluid culture results. Ten patients had positive cerebrospinal fluid cultures, eight of which yielded Staphylococcus species, and one each Acinetobacter and Pseudomonas. Cerebrospinal fluid TNF-alpha, IL-1 beta, IL-6, protein, and leukocyte concentrations were significantly increased in patients with shunt infection. Cerebrospinal fluid IL-6 activity had the highest diagnostic accuracy of the cytokines evaluated, with sensitivity of 80% and specificity of 98%.
The presence of cerebrospinal fluid inflammatory cytokines strongly suggests ventriculoperitoneal shunt infection. Detection of these cytokines in the cerebrospinal fluid could be used for earlier diagnosis of bacterial infection.
Proinflammatory mediators that include tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) and anti-inflammatory mediators such as interleukin-10 (IL-10) modulate ...the immune response to endotoxemia. IL-10 downregulates the production of TNF-alpha and MIP-2. Acute lung injury may occur secondary to neutrophil chemotaxis mediated by chemokine MIP-2. We studied the temporal relationship of TNF-alpha, MIP-2, and IL-10 in rat endotoxemia and correlation of MIP-2 concentrations with acute lung injury.
Ten ventilated rats were randomized to receive an intravenous infusion of 2 mg/kg Escherichia coli lipopolysaccharide (n = 6) or saline placebo (n = 4). Blood pressure was continuously monitored and arterial blood was obtained for lactate, blood gas, TNF-alpha, IL-10, and MIP-2 measurements at baseline, 2, 4, and 5.5 hours after LPS or saline infusion.
Endotoxemia resulted in hypotension, lactic acidemia, and increased alveolar-arterial oxygen gradient (A-a O2 gradient) compared with the placebo group. TNF-alpha, MIP-2, and IL-10 levels were increased 2 hours after endotoxemia. Subsequently, TNF-alpha levels declined while IL-10 and MIP-2 levels remained elevated. Control rats had no significant increase in cytokine production at any time point. MIP-2 concentrations correlated with A-a O2 gradient, an indicator of lung injury (r = 0.56, p < 0.001).
MIP-2, possibly released by TNF-alpha stimulation of macrophages, is associated with acute lung injury possibly by inducing neutrophil chemotaxis. IL-10 may exert its counter-inflammatory response by inhibiting the release of TNF-alpha in endotoxemia.
Astemizole, a relatively new H1 blocker, has been reported to cause ventricular arrhythmias in the poisoned patient. We present two cases of astemizole poisoning, one with asystole followed by ...ventricular fibrillation occurring 11 hours after ingestion treated with defibrillation and one with an isolated finding of a prolonged corrected QT interval. Electrocardiogram monitoring to detect conduction defects can identify patients at risk of developing life-threatening arrhythmias.
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