Marc Robin Mendler

Effects of Automated Adjustment of the Inspired Oxygen on Fluctuations of Arterial and Regional Cerebral Tissue Oxygenation in Preterm Infants with Frequent Desaturations

OBJECTIVE To assess the effect of automated adjustment of the inspired oxygen fraction (FiO2) on arterial oxygen saturation (SpO2) and cerebral tissue oxygen saturation (SctO2) in very low birth weight infants with frequent fluctuations in oxygenation. STUDY DESIGN Fifteen infants (median gestational age, 25 weeks [range, 23-28 weeks]; median age, 34 days [range, 19-74 days]) were assigned in random sequence to 24 hours of automated adjustment of FiO2 or manual adjustment of FiO2. Primary outcome measurements were time within the SpO2 target range and the area under the curve above and below a defined SctO2 range. RESULTS Percentage of time within the SpO2 target range increased during automated FiO2 control (76.3% ± 9.2% vs 69.1% ± 8.2% for manual; P < .01). Prolonged episodes with SpO2 <88% of >60 seconds duration (median, 115 episodes [range, 67-240] vs 54 episodes [range, 7-184]; P < .01) and of >180 seconds duration (median, 13 episodes [range, 6-39] vs 2 episodes [range, 0-5]; P < .01) decreased significantly during the automated period. Percentage of time with SpO2 >96% decreased during automated control (6.6% ± 4.4% vs 10.4% ± 3.3%; P < .02). There was no significant difference in FiO2 exposure. The area (deviation × time) below and above the defined SctO2 threshold did not differ between the 2 periods (median, 59.7%*seconds [range, 17.2%-208.3%] for manual vs 49.0%*seconds [range, 4.3%-193.7%] for automated; P = .36). CONCLUSION Automated FiO2 control in preterm infants with frequent SpO2 fluctuations significantly increased the time within the SpO2 target range and reduced the incidence of prolonged hypoxemic events compared with manual FiO2 adjustment, but did not significantly affect cerebral tissue oxygenation.

Very Low Tidal Volume Ventilation with Associated Hypercapnia - Effects on Lung Injury in a Model for Acute Respiratory Distress Syndrome

Background Ventilation using low tidal volumes with permission of hypercapnia is recommended to protect the lung in acute respiratory distress syndrome. However, the most lung protective tidal volume in association with hypercapnia is unknown. The aim of this study was to assess the effects of different tidal volumes with associated hypercapnia on lung injury and gas exchange in a model for acute respiratory distress syndrome. Methodology/Principal Findings In this randomized controlled experiment sixty-four surfactant-depleted rabbits were exposed to 6 hours of mechanical ventilation with the following targets: Group 1: tidal volume = 8–10 ml/kg/PaCO2 = 40 mm Hg; Group 2: tidal volume = 4–5 ml/kg/PaCO2 = 80 mm Hg; Group 3: tidal volume = 3–4 ml/kg/PaCO2 = 120 mm Hg; Group 4: tidal volume = 2–3 ml/kg/PaCO2 = 160 mm Hg. Decreased wet-dry weight ratios of the lungs, lower histological lung injury scores and higher PaO2 were found in all low tidal volume/hypercapnia groups (group 2, 3, 4) as compared to the group with conventional tidal volume/normocapnia (group 1). The reduction of the tidal volume below 4–5 ml/kg did not enhance lung protection. However, oxygenation and lung protection were maintained at extremely low tidal volumes in association with very severe hypercapnia and no adverse hemodynamic effects were observed with this strategy. Conclusion Ventilation with low tidal volumes and associated hypercapnia was lung protective. A tidal volume below 4–5 ml/kg/PaCO2 80 mm Hg with concomitant more severe hypercapnic acidosis did not increase lung protection in this surfactant deficiency model. However, even at extremely low tidal volumes in association with severe hypercapnia lung protection and oxygenation were maintained.

Effects of Synchronization during Noninvasive Intermittent Mandatory Ventilation in Preterm Infants with Respiratory Distress Syndrome Immediately after Extubation.

Background: Noninvasive ventilation is increasingly used in very-low-birth-weight infants (VLBWI) to reduce complications that occur with invasive ventilation. However, the physiological effects of synchronization during noninvasive nasal intermittent mandatory ventilation (IMV) have not been tested in VLBWI immediately after extubation. Objective: We aimed to study the short-term effects of synchronized nasal IMV (S-NIMV) compared to nonsynchronized nasal IMV (NIMV) on breathing effort as measured by phasic esophageal pressure (Pe) deflection, spontaneous respiratory rate (RR), gas exchange, cerebral tissue oxygen saturation (StO2) and intermittent episodes of bradycardia or hypoxemia in VLBWI recovering from respiratory distress syndrome (RDS). Methods: Fourteen VLBWI recovering from RDS were studied using a randomized cross-over design during both S-NIMV and NIMV (of 2 h each) immediately after extubation. Results: Phasic Pe deflection, spontaneous RR and transcutaneous PCO2 decreased significantly while transcutaneous PO2 and synchrony rate (defined as peak ventilator pressure delivered within the first half of spontaneous inspiration) increased significantly during S-NIMV compared to during NIMV. There was no difference in blood pressure, average arterial oxygen saturation (SpO2), cerebral StO2, fractional tissue oxygen extraction of the brain and severe bradycardia (defined as time with a heart rate <100 beats/min lasting ≥10 s) and in hypoxemic episodes (SpO2 <80%) between the two modes. Conclusion: Synchronization during nasal ventilation immediately after extubation in VLBWI recovering from RDS improved gas exchange and decreased the respiratory effort, and it could therefore be considered to provide a more efficient respiratory support and synchrony.

Effect of Different Respiratory Modes on Return of Spontaneous Circulation in a Newborn Piglet Model of Hypoxic Cardiac Arrest.

Background: There are no clear evidence-based recommendations on the use of different techniques of respiratory support and chest compressions (CC) during neonatal cardiopulmonary resuscitation (CPR). Objectives: To determine the effects of different respiratory support strategies along with CC representing clinical practice on the return of spontaneous circulation (ROSC) in hypoxic newborn piglets with cardiac arrest. We hypothesized that use of a T-piece resuscitator (TPR) providing positive end-expiratory pressure (PEEP) reduces time to ROSC as compared to a self-inflating bag (SIB) without PEEP. Furthermore, we explored the effects of a ventilator providing inflations without synchrony to CC. Methods: Thirty-three newborn piglets were exposed to hypoxia until asystole occurred and randomized into three groups and resuscitated according to ILCOR guidelines: group 1 = TPR [peak inspiratory pressure (PIP)/PEEP of 25/5 cm H2O, rate 30/min], inflations interposed between CC (3:1 ratio); group 2 = SIB (PIP of 25 cm H2O without PEEP, rate 30/min), inflations interposed between CC (3:1 ratio), and group 3 = ventilator (PIP/PEEP of 25/5 cm H2O, rate 30/min), CC were applied with a rate of 120/min without synchrony to inflations. Animals were supported for 120 min after ROSC. Primary outcome was time to ROSC. Results: All animals achieved ROSC. We found no significant difference in time to ROSC between groups [median (IQR); TPR: 150 s (150-210); SIB: 150 s (120-180); ventilator: 180 s (150-345)]. There was no difference in use of epinephrine, in blood gases or hemodynamic parameters during the 120-min observation time after ROSC. Conclusions: We found no significant effect of different respiratory support strategies during CPR on ROSC.

Reliability of Pulse Oximetry during Cardiopulmonary Resuscitation in a Piglet Model of Neonatal Cardiac Arrest

Background: Pulse oximetry is widely used in intensive care and emergency conditions to monitor arterial oxygenation and to guide oxygen therapy. Objective: To study the reliability of pulse oximetry in comparison with CO-oximetry in newborn piglets during cardiopulmonary resuscitation (CPR). Methodology: In a prospective cohort study in 30 healthy newborn piglets, cardiac arrest was induced, and thereafter each piglet received CPR for 20 min. Arterial oxygen saturation was monitored continuously by pulse oximetry (SpO2). Arterial blood was analyzed for functional oxygenation (SaO2) every 2 min. SpO2 was compared with coinciding SaO2 values and bias considered whenever the difference (SpO2 - SaO2) was beyond ±5%. Results: Bias values were decreased at the baseline measurements (mean: 2.5 ± 4.6%) with higher precision and accuracy compared with values across the experiment. Two minutes after cardiac arrest, there was a marked decrease in precision and accuracy as well as an increase in bias up to 13 ± 34%, reaching a maximum of 45.6 ± 28.3% after 10 min over a mean SaO2 range of 29-58%. Conclusion: Pulse oximetry showed increased bias and decreased accuracy and precision during CPR in a model of neonatal cardiac arrest. We recommend further studies to clarify the exact mechanisms of these false readings to improve reliability of pulse oximetry during the marked desaturation and hypoperfusion found during CPR.

A minimal model of burst-noise induced bistability

We investigate the influence of intrinsic noise on stable states of a one-dimensional dynamical system that shows in its deterministic version a saddle-node bifurcation between monostable and bistable behaviour. The system is a modified version of the Schlögl model, which is a chemical reaction system with only one type of molecule. The strength of the intrinsic noise is varied without changing the deterministic description by introducing bursts in the autocatalytic production step. We study the transitions between monostable and bistable behavior in this system by evaluating the number of maxima of the stationary probability distribution. We find that changing the size of bursts can destroy and even induce saddle-node bifurcations. This means that a bursty production of molecules can qualitatively change the dynamics of a chemical reaction system even when the deterministic description remains unchanged.

Tidal Volume Delivery and Endotracheal Tube Leak during Cardiopulmonary Resuscitation in Intubated Newborn Piglets with Hypoxic Cardiac Arrest Exposed to Different Modes of Ventilatory Support

Background: There are few data available on the interaction of inflations, chest compressions (CC), and delivery of tidal volumes in newborn infants undergoing resuscitation in the presence of endotracheal tube (ET) leaks. Objectives: To determine the effects of different respiratory support strategies along with CC on changes in tidal volume and ET leaks in hypoxic newborn piglets with cardiac arrest. Methods: Asphyxiated newborn piglets, intubated with weight-adapted uncuffed ET, were randomized into three groups and resuscitated according to ILCOR 2010 guidelines: (1) T-piece resuscitator (TPR) group = peak inspiratory pressure (PIP)/positive end-expiratory pressure (PEEP) 25/5 cm H2O, rate 30/min, inflations interposed between CC (3:1 ratio); (2) self- inflating bag (SIB) group = PIP 25 cm H2O without PEEP, rate 30/min, inflations interposed between CC (3:1 ratio), and (3) ventilator group = PIP/PEEP of 25/5 cm H2O, rate 30/min. CC were applied with a rate of 120/min without synchrony to inflations. Results: We observed a significant increase of leak (average increase 11.4%) when CC was added to respiratory support (p = 0.0001). Expired tidal volume was larger in the SIB group than in the two other modes which both applied PEEP. However, tidal volumes caused by CC only were larger in the two groups with PEEP than in the SIB group (without PEEP). Conclusions: There is interaction between lung inflations and CC affecting leak and delivery of tidal volume, which may be influenced by the mode/device used for respiratory support. Leak is larger in the presence of PEEP. However, CC cause additional tidal volume which is larger in the presence of PEEP.

Different Techniques of Respiratory Support Do Not Significantly Affect Gas Exchange during Cardiopulmonary Resuscitation in a Newborn Piglet Model

Background: There are no evidence-based recommendations on the use of different techniques of respiratory support and chest compressions (CC) during neonatal cardiopulmonary resuscitation (CPR). Objectives: We studied the short-term effects of different ventilatory support strategies along with CC representing clinical practice on gas exchange [arterial oxygen saturation (SaO2), arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2)], hemodynamics and cerebral oxygenation. We hypothesized that in newborn piglets with cardiac arrest, use of a T-piece resuscitator (TPR) providing positive end-expiratory pressure (PEEP) improves gas exchange as measured by SaO2 during CPR as compared to using a self-inflating bag (SIB) without PEEP. Furthermore, we explored the effects of a mechanical ventilator without synchrony to CC. Methods: Thirty newborn piglets with asystole were randomized into three groups and resuscitated for 20 min [fraction of inspired oxygen (FiO2) = 0.21 for 10 min and 1.0 thereafter]. Group 1 received ventilation using a TPR [peak inspiratory pressure (PIP)/PEEP of 20/5 cm H2O, rate 30/min] with inflations interposed between CC (3:1 ratio). Group 2 received ventilation using a SIB (PIP of 20 cm H2O without PEEP, rate 30/min) with inflations interposed between CC (3:1 ratio). Group 3 received ventilation using a mechanical ventilator (PIP/PEEP of 20/5 cm H2O, rate 30/min). CC were applied with a rate of 120/min without synchrony to inflations. Results: We found no significant differences in SaO2 between the three groups. However, there was a trend toward a higher SaO2 [TPR: 28.0% (22.3-40.0); SIB: 23.7% (13.4-52.3); ventilator: 44.1% (39.2-54.3); median (interquartile range)] and a lower PaCO2 [TPR: 95.6 mm Hg (82.1-113.6); SIB: 100.8 mm Hg (83.0-108.0); ventilator: 74.1 mm Hg (68.5-83.1); median (interquartile range)] in the mechanical ventilator group. Conclusions: We found no significant effect on gas exchange using different respiratory support strategies during CPR.

Analysis of stochastic bifurcations with phase portraits

We propose a method to obtain phase portraits for stochastic systems. Starting from the Fokker-Planck equation, we separate the dynamics into a convective and a diffusive part. We show that stable and unstable fixed points of the convective field correspond to maxima and minima of the stationary probability distribution if the probability current vanishes at these points. Stochastic phase portraits, which are vector plots of the convective field, therefore indicate the extrema of the stationary distribution and can be used to identify stochastic bifurcations that change the number and stability of these extrema. We show that limit cycles in stochastic phase portraits can indicate ridges of the probability distribution, and we identify a novel type of stochastic bifurcation, where the probability maximum moves to the edge of the system through a gap between the two nullclines of the convective field.

Predictive Value of Thompson-Score for Long-Term Neurological and Cognitive Outcome in Term Newborns with Perinatal Asphyxia and Hypoxic-Ischemic Encephalopathy Undergoing Controlled Hypothermia Treatment

Background: The so-called Thompson-score (TS) for newborns with hypoxic-ischemic encephalopathy (HIE) was developed before the introduction of controlled hypothermia as clinical routine. Information on the predictive value of TS in newborns undergoing therapeutic hypothermia to estimate long-term outcome is limited. Objectives: To determine the predictive value of TS to estimate long-term cognitive and neurological outcome in newborns with perinatal asphyxia treated with controlled hypothermia. Methods: Thirty-six term newborns with HIE undergoing controlled hypothermia were followed using Wechsler Preschool and Primary Scale of intelligence III test and standardized neurological examination. The primary outcome was survival without cognitive impairment, defined as an IQ ≥85. Secondary outcomes were motor outcomes, survival without relevant neurological impairment, death and epilepsy. Results: Follow-up was done in 33 out of 36 (91.6%) infants at 53 ± 12 months (mean ± SD). For all investigated parameters, a statistically significant relationship with peak TS was demonstrated. A one-point increase in peak TS indicated an OR (95% CI) of 1.5 (1.1–2.0, p = 0.006) for death or cognitive impairment, an OR (95% CI) of 2.2 (1.3–3.8, p = 0.004) for death or relevant neurologic impairment, an OR (95% CI) of 2.1 (1.3–3.5, p = 0.005) for death or epilepsy and an OR (95% CI) of 1.5 (1.1–2.1, p = 0.02) for death. Although the TS for newborns with adverse outcome (death or cognitive impairment) compared to normal outcome tended to be higher (13 [4–16] vs. 9 [0–13], d1; 15 [5–19] vs. 9 [1–14], d2; 14 [5–21] vs. 8 [2–15], d3; median [range]), there was a considerable overlap during the first 3 days of life between both groups. Conclusions: The TS seems to be a prognostic tool for predicting the long-term outcome in asphyxiated term newborns undergoing controlled hypothermia after the third day of life. A higher score appears to be significantly associated with an adverse outcome.