Utilising pneuRIP device in determining the adequacy of respiratory support when weaning high-flow nasal cannula in paediatric patients with acute respiratory distress: A pilot study.

AIM: Recognition of paediatric respiratory distress and timely intervention is critical, especially during the weaning phase of support in paediatric acute respiratory failure, as weaning too aggressively can lead to further setbacks in a patient's recovery. We aimed to determine if pulmonary function measurements obtained with the pneuRIP device, a noninvasive pulmonary function testing device that provides measurements of labored breathing index (LBI), phase angle and %rib cage (%RC) contribution to breathing, will provide predictive values to assess the adequacy of respiratory support while weaning from HFNC. METHODS: We reviewed patients ages 0-18 years admitted to the PICU for respiratory distress due to respiratory infections receiving HFNC. Patients with history of chronic lung disease and chronic neuromuscular disease with baseline habnormal breathing patterns were excluded. Phase angle, LBI and %RC were obtained every hour and with every wean of HFNC. Nine patients were enroled. RESULTS: Mean LBI range remained 1.27-1.68 when LBI was plotted as a function of the HFNC flow rate. Mean values of %RC contribution to breathing ranged 43.65-57.12 as a function of the HFNC flow rate. No significant deviations existed in either %RC (P = 0.16) or LBI (P = 0.16) during the weaning of HFNC. Mean phase angle for all subjects was 41.48°-74.12° for the duration of wean and showed significant deviation from baseline during the weaning process (p = 0.001). CONCLUSIONS: Measurements of LBI and %RC on the pneuRIP device effectively demonstrated tolerance of weaning HFNC during the recovery phase of acute respiratory failure from a respiratory infection.

Impact of intravenous fluid administration on cardiac output and oxygenation during cardiopulmonary resuscitation.

BACKGROUND: The effect of intravenous fluid (IVF) administration during cardiopulmonary resuscitation (CPR) is an unexplored factor that may improve cardiac output (CO) during CPR. The aim of this study was to determine the effect of IVF administration on CO and oxygenation during CPR. METHODS: This experimental animal study was performed in a critical care animal laboratory. Twenty-two Landrace-Yorkshire female piglets weighing 27-37 kg were anesthetized, intubated, and placed on positive pressure ventilation. Irreversible cardiac arrest was induced with bupivacaine. CPR was performed with a LUCAS 3 mechanical compression device. Pigs were randomized into IVF or no-IVF groups. Pigs in the IVF group were given 20 mL/kg of Plasma-Lyte (Baxter International, Deerfield, IL USA), infused from 15 to 35 min of CPR. CPR was maintained for 50 min with serial measurements of CO obtained using ultrasound dilution technology and partial pressure of oxygen (PaO2). RESULTS: A mixed-effects repeated measures analysis of variance was used to compare within-group, and between-group mean changes in CO and PaO2 over time. CO and PaO2 for the piglets were measured at 10-min intervals during the 50 min of CPR. CO was greater in the IVF compared with the control group at all time points during and after the infusion of the IVF. Mean PaO2 decreased with time; however, at no time was there a significant difference in PaO2 between the IVF and control groups. CONCLUSIONS: Administration of IVF during CPR resulted in a significant increase in CO during CPR both during and after the IVF infusion. There was no statistically significant decrease in PaO2 between the IVF and control groups.

Effect of positive end-expiratory pressure on additional passive ventilation generated by CPR compressions in a porcine model.

BACKGROUND: Compressions given during cardiopulmonary resuscitation generate small, ineffective passive ventilations through oscillating waves. Positive end-expiratory pressure increases the volume of these passive ventilations; however, its effect on passive ventilation is unknown. Our objective was to determine if increasing positive end-expiratory pressure during cardiopulmonary resuscitation increases passive ventilation generated by compressions to a clinically significant point. This study was conducted on 13 Landrace-Yorkshire pigs. After inducing cardiac arrest with bupivacaine, cardiopulmonary resuscitation was performed with a LUCAS 3.1. During cardiopulmonary resuscitation, pigs were ventilated at a positive end-expiratory pressure of 0, 5, 10, 15, 20 cmH2O (randomly determined) for 9 min. Using the NM3 respiratory monitoring device, expired minute ventilation and volumetric capnography were measured. Arterial blood gas was obtained for each positive end-expiratory pressure level to compare the effects of positive end-expiratory pressure on carbon dioxide. RESULTS: Increasing positive end-expiratory pressure from 0 to 20 cmH2O increased the mean (SEM) expired minute ventilation from 6.33 (0.04) to 7.33 (0.04) mL/min. With the 5-cmH2O incremental increases in positive end-expiratory pressure from 0 to 20 cmH2O, volumetric capnography increased from a mean (SEM) of 94.19 (0.78) to 115.18 (0.8) mL/min, except for 15 cmH2O, which showed greater carbon dioxide exhalation with volumetric capnography compared with 20 cmH2O. PCO2 declined significantly as positive end-expiratory pressure was increased from 0 to 20 cmH2O. CONCLUSIONS: When increasing positive end-expiratory pressure from 0 to 20, the contribution to overall ventilation from gas oscillations generated by the compressions became more significant, and may even lead to hypocapnia, especially when using positive end-expiratory pressures between 15 and 20.

Use of pulse contour technology for continuous blood pressure monitoring in pediatric patients.

OBJECTIVES: This study evaluates the accuracy of continuous blood pressure monitoring using pulse contour technology with the ClearSight monitoring device, a noninvasive alternative to placing an invasive arterial line, in pediatric patients. METHODS: Children younger than 18 years admitted to a pediatric ICU, who required an arterial line, and fit into the ClearSight finger cuff were included. Blood pressure measurement for systolic, diastolic, and mean arterial pressures (MAP) obtained by the ClearSight device were compared with those obtained with the intra-arterial catheter as well as automated cuff measurements using the mixed-effects model. Analysis was conducted for entire cohort, and measurements obtained with and without vasopressor use. RESULTS: There were 213 measurements from 10 patients. There was a statistically significant difference in systolic blood pressure when comparing arterial line and ClearSight systolic and diastolic measurements between the two methods (P < 0.001). There was no statistical difference between arterial MAP and ClearSight MAP (P = 0.957). Results were similar when ClearSight measurements were compared with automated cuff measurements. Both the vasopressor use and nonvasopressor use groups showed a statistically significant difference between arterial and ClearSight measurements for systolic and diastolic pressures, but not for the MAP. CONCLUSIONS: Measurements of MAP obtained by the ClearSight device were almost identical to those obtained by the intra-arterial catheter. Although there was a difference in systolic blood pressures between the two methods, in those patients receiving inotropic support, the difference was within the range of what is considered acceptable in validating blood pressure devices.

The effect of positive end-expiratory pressure on cardiac output and oxygen delivery during cardiopulmonary resuscitation.

BACKGROUND: Positive end-expiratory pressure (PEEP) is used to optimize oxygenation by preventing alveolar collapse. However, PEEP can potentially decrease cardiac output through cardiopulmonary interactions. The effect of PEEP on cardiac output during cardiopulmonary resuscitation (CPR) is not known. METHODS: This was a preclinical randomized, controlled, animal study conducted in an animal research facility on 25 Landrace-Yorkshire pigs. After inducing cardiac arrest, CPR was performed with LUCAS 3. During CPR, pigs were ventilated at a PEEP of 0, 5, 10, 15, 20 cmH2O (randomly determined via lottery) for 9 min. Cardiac output, obtained via ultrasound dilution, and PaO2 were measured, and oxygen delivery calculated for each PEEP. RESULTS: A mixed-effects repeated-measures analysis of variance was used to compare the baseline value adjusted mean cardiac output, PaO2, and oxygen delivery between PEEP groups. Least significant difference test was used to conduct pairwise comparisons between PEEP groups. To determine optimum PEEP, Gaussian mixture model was applied to the adjusted means of cardiac output and oxygen delivery. Increasing PEEP to 10 and higher resulted in significant declines in cardiac output. A PEEP of 15 and higher resulted in significant declines in oxygen delivery. As PEEP was increased from 0 to 20, PaO2 increased significantly. Gaussian mixture model identified the 0-5 PEEP group as providing optimal cardiac output and oxygen delivery, with PEEP of 5 providing the highest oxygen delivery. CONCLUSIONS: A PEEP of 0-5 resulted in the optimal oxygen delivery and cardiac output during CPR, with PEEP of 5 resulting in higher oxygen delivery, and a slightly lower, statistically insignificant cardiac output than PEEP of 0.

Phosphorylation of caspase-9 in the cytosolic fraction of the cerebral cortex of newborn piglets following hypoxia.

We have previously shown that hypoxia leads to increased expression and increased activity of caspase-9 in the cerebral cortex of newborn piglets. Previous studies have demonstrated the importance of caspase-9 in the initiation of the apoptotic cascade, however, the mechanism of caspase-9 activation is not well understood. Experiments were conducted on newborn piglets 2-3 days of age that were anesthetized and mechanically ventilated. Hypoxia was induced by lowering the FiO(2) to 0.05-0.07 x 1h, and was confirmed biochemically by demonstrating decreased levels of ATP and PCr in the hypoxic groups in comparison with the normoxic group. The ATP level was 1.99+/-0.66 in the hypoxic group versus 4.10+/-0.19 in the normoxic group, P<0.05, and the PCr value was 0.68+/-0.14 in the hypoxic group, compared to 2.98+/-0.39 in the normoxic group, P<0.05. The cytosol of the neuronal nuclei from the cerebral cortex was probed with anti-phosphorylated Ser(196) caspase-9 antibody, using Western blot analysis. Protein bands were analyzed using image densitometry. In both the hypoxic and normoxic samples, protein bands were demonstrated just above the 50 kDa marker. Phosphorylated caspase-9 expression in OD x mm(2) was 43.85+/-8.4 in the normoxic group and 67.6+/-9.88 in the hypoxic group, P<0.05. The results of this study demonstrate that caspase-9, a key protein in hypoxia induced apoptosis, is phosphorylated at the Ser(196) site during hypoxia. The results demonstrate that hypoxia results in a post-translational modification of caspase-9 at Ser(196), which may alter the activity of caspase-9 in the hypoxic newborn brain.

Impact of Obesity on Outcomes in Critically Ill Children.

PURPOSE: To examine whether obesity confers a protective effect on critically ill pediatric patients, similar to what has been reported in critically ill adults. METHODS: A retrospective cohort study including patients aged 2-18 years admitted to a 24-bed pediatric intensive care unit from 2009 to 2014. Patients were divided into 1 of 3 weight categories: normal weight (body mass index [BMI], 5%-84.9%), overweight (BMI, 85%-94.9%), and obese (BMI ≥95%). Outcomes investigated included mortality, need for intubation, need for inotropic support, and duration of mechanical ventilation. RESULTS: A total of 1817 patient encounters met inclusion criteria. There was no difference in Pediatric Index of Mortality 2 scores between groups. There was a significantly smaller percentage of overweight and obese patients requiring intubation ( P = .003) and inotropic support ( P = .031) compared with normal-weight patients. Being overweight or obese was neither protective nor a risk factor for mortality with an adjusted odds ratio of 1.83 (confidence interval [CI], 0.82-3.85; P = .12) and 1.51 (CI, 0.70-3.12; P = .27) comparing the overweight and obese groups with the normal-weight group, respectively. There was no difference in duration of mechanical ventilation between the normal-weight and overweight and obese groups ( P = .893 and 0.484, respectively). CONCLUSIONS: In critically ill pediatric patients, being overweight or obese was associated with decreased need for intubation and inotropic support compared with normal-weight patients. However, being overweight or obese is neither protective nor a risk factor for mortality or duration of mechanical ventilation.

22q11.2 Deletion syndrome is associated with increased perioperative events and more complicated postoperative course in infants undergoing infant operative correction of truncus arteriosus communis or interrupted aortic arch.

OBJECTIVE: The effect of genotype on the outcomes of infant cardiac operations has not been well established. The purpose of the present study was to investigate the effect of 22q11.2 deletion (22q11del) on infants with truncus arteriosus communis (TA) and interrupted aortic arch (IAA) undergoing operative correction during infancy. METHODS: We conducted a retrospective cohort study of all infants who had undergone operative correction of TA or IAA at the Children's Hospital of Philadelphia from 1995 to 2007, comparing the perioperative outcomes (hospital length of stay, intensive care, mechanical ventilation, risk of cardiac and noncardiac events, number of consultations, and number of discharge medications) by 22q11del status. RESULTS: A total of 104 patients were studied (55 with TA and 49 with IAA), of whom 40 (38%) were 22q11del positive. The 22q11del status was unknown in 9 (7 with TA and 2 with IAA). In patients with known deletion status, those with 22q11del had a longer hospital and intensive care length of stay. Subjects with 22q11del also required more frequent operative reintervention and more consultations and were prescribed more medications at discharge. No significant difference was found in method of feeding between those with and without 22q11del at discharge. CONCLUSIONS: In this study, 22q11del is associated with perioperative outcomes in infants undergoing operative correction of TA and IAA, with longer hospital stays and greater resource utilization in the perioperative period. These findings should inform counseling and risk stratification and warrant additional study to identify genotype-specific management strategies to improve outcomes.

Use of insulin to decrease septic shock-induced myocardial depression in a porcine model.

Insulin is known to attenuate septic shock-induced myocardial depression. Possible mechanisms include an anti-inflammatory or inotropic effect of insulin. The objective of this study was to determine whether the mechanism of action of insulin in attenuating septic shock-induced myocardial depression is through an immunomodulatory effect. Fourteen pigs were assigned to one of two groups. Both groups received a 4-h infusion of lipopolysaccharide endotoxin from Escherichia coli 0111:B4. Group 2 additionally received insulin at 1.5 U/kg/h with infusions of D50 normal saline and KCl to maintain normal serum glucose and potassium levels. Cardiac function was measured with shortening fraction using transthoracic echocardiogram. Plasma TNF-α, IL-1ß, and IL-6 levels were obtained every 30 min. Postmortem cytokine analysis and histomorphology were performed on the heart tissue. Although insulin attenuated septic shock-induced myocardial depression, this was not due to an anti-inflammatory effect and, therefore, likely resulted from an inotropic effect of insulin.

Outcome after two-patch repair of complete common atrioventricular canal defects in patients weighing four kilograms or less.

BACKGROUND: Early repair of a complete common atrioventricular canal defect (CCAVCD) may benefit patients who exhibit congestive heart failure and failure to thrive. However, concern about increased risk and fragility of valve tissue has commonly led to delaying the surgical repair until the patients achieve a predetermined weight. We report our experience with a strategy of early repair independent of age or weight. METHODS: Between 2003 and 2009, 32 patients underwent two-patch repair of CCAVCD at our institution; 22 patients weighed between 2.5 and 4 kg (group #1) and 10 weighed more than 4 kg (group #2). Medical records and echocardiographic studies were reviewed to determine whether there was a difference in the incidence of mortality, rate of reintervention, and complications between the two groups. RESULTS: Operative mortality was 3.1% (1 of 32), with one additional death two years after repair, for an overall mortality of 6.25%. Median duration of mechanical ventilation, median hospital stay, and intropic score was similar between both groups. Freedom from valve reintervention was 91% in group #1 (20 of 22), and 89% in group #2 (8 of 9, p = 1.00). CONCLUSIONS: Complete common atrioventricular canal defect can be repaired safely and effectively in patients under 4 kg. Although mortality was not increased, smaller patients have a tendency for longer intensive care and hospital stay as well as a higher incidence of atrioventricular valve regurgitation. However, valve function improved during the period of follow-up and did not impact the freedom from reintervention.