S Schumann

Electrical impedance tomography to confirm correct placement of double-lumen tube: a feasibility study

BACKGROUNDnDouble-lumen tubes (DLTs) are frequently used to establish one-lung ventilation (OLV). Their correct placement is crucial. We hypothesized that electrical impedance tomography (EIT) reliably displays distribution of ventilation between left and right lung and may thus be used to verify correct DLT placement online.nnnMETHODSnRegional ventilation was studied by EIT in 40 patients requiring insertion of left-sided DLTs for OLV during thoracic surgery. EIT was recorded during two-lung ventilation before induction of anaesthesia and after DLT placement, and during OLV in the supine and subsequently in the lateral position. EIT measurements were made before and after verification of correct DLT placement by fibreoptic bronchoscopy (FOB).nnnRESULTSnEIT accurately displayed distribution of ventilation between left and right lung online. All cases (n=5) of initially misplaced DLTs in the contralateral right main bronchus were detected by EIT. However, EIT did not allow prediction of FOB-detected endobronchial cuff misplacement requiring DLT repositioning. Furthermore, after DLT repositioning, distribution of ventilation, as assessed by EIT, did not change significantly (all P>0.5).nnnCONCLUSIONSnThis study demonstrates that EIT enables accurate display of left and right lung ventilation and, thus, non-invasive online recognition of misplacement of left-sided DLTs in the contralateral main bronchus. However, as distribution of ventilation did not correlate with endobronchial cuff placement, EIT cannot replace FOB in the routine control of DLT position.

Flow-controlled expiration: a novel ventilation mode to attenuate experimental porcine lung injury

BACKGROUNDnWhereas the effects of various inspiratory ventilatory modifications in lung injury have extensively been studied, those of expiratory ventilatory modifications are less well known. We hypothesized that the newly developed flow-controlled expiration (FLEX) mode provides a means of attenuating experimental lung injury.nnnMETHODSnExperimental acute respiratory distress syndrome was induced by i.v. injection of oleic acid in 15 anaesthetized and mechanically ventilated pigs. After established lung injury ([Formula: see text]ratio <27 kPa), animals were randomized to either a control group receiving volume-controlled ventilation (VCV) or a treatment group receiving VCV with additional FLEX (VCV+FLEX). At predefined times, lung mechanics and oxygenation were assessed. At the end of the experiment, the pigs were killed, and bronchoalveolar fluid and lung biopsies were taken. Expression of inflammatory cytokines was analysed in lung tissue and bronchoalveolar fluid. Lung injury score was determined on the basis of stained tissue samples.nnnRESULTSnCompared with the control group (VCV; n=8), the VCV+FLEX group (n=7) demonstrated greater dynamic lung compliance and required less PEEP at comparable [Formula: see text] (both P<0.05), had lower regional lung wet-to-dry ratios and lung injury scores (both P<0.001), and showed less thickening of alveolar walls (an indicator of interstitial oedema) and de novo migration of macrophages into lung tissue (both P<0.001).nnnCONCLUSIONSnThe newly developed FLEX mode is able to attenuate experimental lung injury. FLEX could provide a novel means of lung-protective ventilation.

Leakage in nasal high‐frequency oscillatory ventilation improves carbon dioxide clearance—A bench study

Objective: Nasal high frequency oscillatory ventilation (nHFOV) is a promising mode of non‐invasive neonatal respiratory support. To combine the effects of nasal continuous positive airway pressure (nCPAP) and high frequency oscillatory ventilation, an oscillatory pressure waveform is superposed to a nCPAP via a nasal or nasopharyngeal interface. nHFOV has been described to facilitate carbon dioxide (CO2) elimination compared to nCPAP. The influence of unintended leakage on CO2 elimination has not been investigated in nHFOV before. We explored the effects of oral leakage on CO2 elimination during nHFOV in a physical model of the neonatal respiratory system. Methods: A neonatal ventilator was connected to an airway‐ and lung model using binasal prongs as interface. The model comprised a continuous CO2 influx. Alveolar CO2 partial pressure was continuously measured. Gas flow rates and pressures were measured simultaneously at the prongs, pharynx, lung, and at the leakage. Effects of combined nasopharyngeal leakage (0, 5, or 10u2009L/min) on CO2 elimination, gas flow rate and pressure were determined at various ventilation frequencies (6, 8, 10, and 12u2009Hz) and amplitudes (10%, 20%, and 30% of maximum ventilator performance) at a mean airway pressure of 10u2009cmH2O. Results: nHFOV with moderate leakage was more effective in CO2 elimination than without leakage (Pu2009<u20090.001) for all tested amplitudes and frequencies. Maximum leakage resulted in highly variable, partly ineffective CO2 elimination. Conclusions: A moderate oral leakage rather improves than impairs gas exchange during non‐invasive ventilatory support with nHFOV. Pediatr Pulmonol. 2017;52:367–372.

Pneumoperitoneum deteriorates intratidal respiratory system mechanics: an observational study in lung-healthy patients

BackgroundPneumoperitoneum during laparoscopic surgery leads to atelectasis and impairment of oxygenation. Positive end-expiratory pressure (PEEP) is supposed to counteract atelectasis. We hypothesized that the derecruiting effects of pneumoperitoneum would deteriorate the intratidal compliance profile in patients undergoing laparoscopic surgery.MethodsIn 30 adult patients scheduled for surgery with pneumoperitoneum, respiratory variables were measured during mechanical ventilation. We calculated the dynamic compliance of the respiratory system (CRS) and the intratidal volume-dependent CRS curve using the gliding-SLICE method. The CRS curve was then classified in terms of indicating intratidal recruitment/derecruitment (increasing profile) and overdistension (decreasing profile). During the surgical interventions, the PEEP level was maintained nearly constant at 7xa0cm H2O. Data are expressed as mean [confidence interval].ResultsBaseline CRS was 60 [54–67]xa0mLxa0cm H2O−1. Application of pneumoperitoneum decreased CRS to 40 [37–43] mLxa0cm H2O−1 which partially recovered to 54 [50–59] mLxa0cm H2O−1 (Pxa0<xa00.001) after removal but remained below the value measured before pneumoperitoneum (Pxa0<xa00.001). Baseline compliance profiles indicated intratidal recruitment/derecruitment in 48xa0% patients. After induction of pneumoperitoneum, intratidal recruitment/derecruitment was indicated in 93xa0% patients (Pxa0<xa00.01), and after removal intratidal recruitment/derecruitment was indicated in 59xa0% patients. Compliance profiles showing overdistension were not observed.ConclusionsAnalyses of the intratidal compliance profiles reveal that pneumoperitoneum during laparoscopic surgery causes intratidal recruitment/derecruitment which partly persists after its removal. The analysis of the intratidal volume-dependent CRS profiles could be used to guide intraoperative PEEP adjustments during elevated intraabdominal pressure.

Cardiogenic oscillations in spontaneous breathing airway signal reflect respiratory system mechanics

Background: Heartbeat‐related pressure oscillations appear at the airway opening. We investigated whether these cardiogenic oscillations (COS) – extracted from spontaneous breathing signals – reflect the compliance of the respiratory system.

Clinical on-site monitoring of ß-lactam antibiotics for a personalized antibiotherapy

An appropriate antibiotherapy is crucial for the safety and recovery of patients. Depending on the clinical conditions of patients, the required dose to effectively eradicate an infection may vary. An inadequate dosing not only reduces the efficacy of the antibiotic, but also promotes the emergence of antimicrobial resistances. Therefore, a personalized therapy is of great interest for improved patients’ outcome and will reduce in long-term the prevalence of multidrug-resistances. In this context, on-site monitoring of the antibiotic blood concentration is fundamental to facilitate an individual adjustment of the antibiotherapy. Herein, we present a bioinspired approach for the bedside monitoring of free accessible ß-lactam antibiotics, including penicillins (piperacillin) and cephalosporins (cefuroxime and cefazolin) in untreated plasma samples. The introduced system combines a disposable microfluidic chip with a naturally occurring penicillin-binding protein, resulting in a high-performance platform, capable of gauging very low antibiotic concentrations (less than 6 ng ml−1) from only 1u2009µl of serum. The system’s applicability to a personalized antibiotherapy was successfully demonstrated by monitoring the pharmacokinetics of patients, treated with ß-lactam antibiotics, undergoing surgery.

Non-invasive high-frequency oscillatory ventilation in preterm infants: a randomised controlled cross-over trial

Objective Non-invasive high-frequency oscillatory ventilation (nHFOV) has recently been described as a novel mode of respiratory support for premature infants. This study was designed to determine whether nHFOV decreases CO2 partial pressure (pCO2) in premature infants more effectively than non-invasive continuous positive airway pressure (nCPAP). Design Non-blinded prospective randomised controlled cross-over study. Setting University Medical Center tertiary neonatal intensive care unit. Patients 26 premature infants of 27±2 weeks of gestational age after extubation or non-invasive surfactant treatment. Interventions Infants were treated with 4u2009hours of nHFOV and 4u2009hours of nCPAP in a cross-over design. The sequence of the ventilation mode was randomly allocated. Main outcome measures The primary outcome measure was pCO2 of arterial or arterialised blood 4u2009hours after commencing the respective mode of respiratory support. Secondary outcome criteria included events of apnoea and bradycardia, respiratory rate, heart rate, pain and/or discomfort, mean airway pressure, fraction of inspired oxygen and failure of non-invasive respiratory support. Results pCO2 after 4u2009hours of nHFOV was similar compared with 4u2009hours of nCPAP (p=0.33). pCO2 was 54.8 (14.6) vs 52.7 (9.3) mm Hg mean (SD) for the nHFOV–nCPAP period (n=13) and 49.0 (8.1) vs 47.7 (9.5) mm Hg for the nCPAP–nHFOV period (n=13). There was no difference in any of the secondary outcome measures. nHFOV was terminated prematurely in five cases for predefined failure criteria (p=0.051). Conclusions We could not demonstrate an increased carbon dioxide clearance applying nHFOV compared with nCPAP in this cohort of preterm infants. Trial registration number DRKS00007171, results.

Biosensors and personalized drug therapy: what does the future hold?

In recent years, personalized medicine (PM), targeting at a tailored drug therapy or preventive care as individualized as the disease itself, is getting increasingly important in human medicine, pharmaceutical, and health-care industry. One of the important concepts of PM is ‘the right drug for the right patient at the right dose and time’ [1]. So, after the decision for a medication, a personalized drug therapy, which customizes the dose, dosage intervals, and the duration of the treatment to cover the patients’ individual needs, is vital. Nowadays, patients receive mostly the same standardized dose of a particular drug, independent of their clinical conditions. Although many different parameters, like health status (e.g. organ functions, infections, and genetic factors), metabolism (e.g. age, sex, and nutrition), or other physical factors (e.g. body weight), play a part in variable drug response, they are often not sufficiently taken into account. The first step toward an individualized drug therapy is therapeutic drug monitoring (TDM), the clinical measurement of medication in a human body fluid (e.g. blood, saliva, or urine) at certain time intervals during the treatment [2]. It aims to keep the drug concentration constantly over a certain threshold value, the so-called minimal inhibitory concentration, in the patient’s bloodstream, while personalizing the drug regimen. In this regard, the (quasi) real-timemonitoring of the pharmacokinetics, which describes all underlying processes (absorption, distribution, metabolism, and elimination) of a drug administered to a living organism, is crucial. Such an approach would be helpful mainly for drugs with narrow therapeutic windows, with known pharmacokinetic variability or with high risk for adverse effects (e.g. toxicity). These include, for example, antibiotics (e.g. aminoglycosides, vancomycin, or ß-lactams), antidepressants, antipsychotics, caffeine (in case of apnea in preterm infants), as well as immunosuppressive, antiarrhythmic (e.g. digoxin), and many antiepileptic agents for chronic therapy [3]. One of the main causes for the pharmacokinetic variability is the diverse renal function of patients as most of the drugs are eliminated by the kidneys. Therefore, the supplemental surveillance of kidney functionality during the pharmacotherapy could also be considered for the further improvement of the personalized drug treatment. The glomerular filtration rate (GFR) is a measure of the renal function. It is commonly gauged by the clearance measurements of exogenous biomarkers (e.g. inulin or iohexol) in urine samples. Yet, these tests are entailed with high running costs and long turnaround times, and therefore, cannot be integrated into clinical routine practice. Moreover, it is very problematic to ensure that the 24-hour urine sample is completely and properly collected by the patients themselves. For this reason, endogenous biomarkers, which are generated at a constant rate and eliminated only by kidneys, will be of great value for GFR testing. Herein, creatinine and cystatin C are considered as suitable candidates [4]. In addition to the TDM, another key aspect is the determination of the therapy duration by measuring predictive and monitoring biomarkers to improve the success and to reduce side effects of the treatment. Especially for the anti-infective therapy (e.g. in sepsis or other infections), near-patient surveillance of the progress of bacterial infections would provide valuable information for PM. In this sense, various biomarkers associated with bacterial inflammation (e.g. cytokines like interleukin-6, or c-reactive protein or procalcitonin) are of great interest [5]. Even the quasi real-time measurement of such biomarkers, indicating the state and progression of the infection, will have a major impact on the patient’s outcome. Additionally, it will allow for the identification of the clinical end point of the disease and thus, the determination of the treatment duration. To meet the needs and challenges of the personalized drug therapy appropriately, the multiplexed on-site monitoring of various substances over time, covering TDM or other therapyrelated issues like renal function or infection status, would be highly desirable. In this sense, biosensors are considered as powerful analytical tools. Since their discovery by Leland C. Clark, Jr. in 1962, biosensors have revolutionized not only the field of health care, but also food and environmental monitoring and so, have greatly improved the quality of our life. Nowadays, pregnancy tests and blood glucose meters are known by everyone since they allow for rapid and easy diagnosis or monitoring, performed at home even by the patients themselves. But how does a biosensor theoretically work? This compact analytical device incorporates a high-affinity recognition element along with a physicochemical transducer. The bioreceptor recognizes a (bio-)chemical event and converts this information into a measurable signal, which is gauged

Respiratory system inertance corresponds to extravascular lung water in surfactant-deficient piglets

In various cardio-pulmonary diseases lung mass is considerably increased due to intrapulmonary fluid accumulation, i.e. extravascular lung water (EVLW). Generally, inertance is a physical system parameter that is mass-dependent. We hypothesized that changes in lung mass influence the inertive behavior of the respiratory system. EVLW and intrathoracic blood volume (ITBV) were compared with respiratory system inertance (I(rs)) in four piglets before and after broncho-alveolar lavage (BAL) that induced surfactant deficiency with interstitial edema. EVLW and ITBV were determined using the double-indicator dilution technique, I(rs) by multiple linear regression analysis. Measurements were taken before, and 1 and 2 h after BAL. EVLW increased threefold (from 6.2+/-0.8 mL/kg at baseline to 17.7+/-0.9 mL/kg (p < 0.001) after BAL). I(rs) increased by 35% (from 0.17+/-0.02 to 0.23+/-0.04 cmH(2)O s(2)/L (p = 0.036) after BAL) and was tightly correlated to EVLW (r(2) = 0.95, p < 0.023). ITBV did not change significantly after BAL. We conclude that I(rs) reflects actual changes in lung mass and thus hints at fluid accumulation within the lung.

Pressure-flow characteristics of breathing systems and their components for pediatric and adult patients

Breathing circuits connect the ventilator to the patients’ respiratory system. Breathing tubes, connectors, and sensors contribute to artificial airway resistance to a varying extent. We hypothesized that the flow‐dependent resistance is higher in pediatric breathing systems and their components compared to respective types for adults.