Christoph Haberthür

Brain metabolism is significantly impaired at blood glucose below 6 mM and brain glucose below 1 mM in patients with severe traumatic brain injury.

IntroductionThe optimal blood glucose target following severe traumatic brain injury (TBI) must be defined. Cerebral microdialysis was used to investigate the influence of arterial blood and brain glucose on cerebral glucose, lactate, pyruvate, glutamate, and calculated indices of downstream metabolism.MethodsIn twenty TBI patients, microdialysis catheters inserted in the edematous frontal lobe were dialyzed at 1 μl/min, collecting samples at 60 minute intervals. Occult metabolic alterations were determined by calculating the lactate- pyruvate (L/P), lactate- glucose (L/Glc), and lactate- glutamate (L/Glu) ratios.ResultsBrain glucose was influenced by arterial blood glucose. Elevated L/P and L/Glc were significantly reduced at brain glucose above 1 mM, reaching lowest values at blood and brain glucose levels between 6-9 mM (P < 0.001). Lowest cerebral glutamate was measured at brain glucose 3-5 mM with a significant increase at brain glucose below 3 mM and above 6 mM. While L/Glu was significantly increased at low brain glucose levels, it was significantly decreased at brain glucose above 5 mM (P < 0.001). Insulin administration increased brain glutamate at low brain glucose, but prevented increase in L/Glu.ConclusionsArterial blood glucose levels appear to be optimal at 6-9 mM. While low brain glucose levels below 1 mM are detrimental, elevated brain glucose are to be targeted despite increased brain glutamate at brain glucose >5 mM. Pathogenity of elevated glutamate appears to be relativized by L/Glu and suggests to exclude insulin- induced brain injury.

Continuous calculation of intratracheal pressure in the presence of pediatric endotracheal tubes.

Objective: To measure the pressure‐flow relationship of pediatric endotracheal tubes (ETTs) in trachea models, to mathematically describe this relationship, and to evaluate in trachea/lung models a method for calculation of pressure at the distal end of the ETT (Ptrach) by subtracting the flow‐dependent pressure drop across the ETT from the airway pressure measured at the proximal end of the ETT. Design: Trachea models and trachea/lung models. Setting: Research laboratory in a university medical center. Interventions: The pressure‐flow relationship of pediatric ETTs (inner diameter, 2.5‐6.5 mm) was determined using a physical model consisting of a tube connector, an anatomically curved ETT, and an artificial trachea. The model was ventilated with sinusoidal gas flow (12‐60 cycles/min). The coefficients of an approximation equation considering ETT resistance and inertance were fitted separately to the measured pressure‐flow curves for inspiration and expiration. Calculated Ptrach was compared with directly measured Ptrach in mechanically ventilated physical trachea/lung models. Measurements and Main Results: The pressure‐flow relationship was considerably nonlinear and showed hysteresis around the origin caused by the inertia of accelerated gas. ETT inertance ranged from 0.1 to 0.4 cm H2O/L·sec2 (inner diameter, 6‐2.5 mm). The abrupt change in cross‐sectional area at the tube connector caused an inspiration‐to‐expiration asymmetry. Calculated and measured Ptrach were within ± 1 cm H2O. Correspondence between measured and calculated Ptrach is improved even further when the ETT inertance is taken into account. Conclusions: Ptrach can continuously be monitored in the presence of pediatric ETT by combining ETT coefficients and the flow and airway pressure continuously measured at the proximal end of the ETT.

Accuracy of automatic tube compensation in new-generation mechanical ventilators.

ObjectiveTo compare performance of flow-adapted compensation of endotracheal tube resistance (automatic tube compensation, ATC) between the original ATC system and ATC systems incorporated in commercially available ventilators. DesignBench study. SettingUniversity research laboratory. SubjectsThe original ATC system, Dräger Evita 2 prototype, Dräger Evita 4, Puritan-Bennett 840. InterventionsThe four ventilators under investigation were alternatively connected via different sized endotracheal tubes and an artificial trachea to an active lung model. Test conditions consisted of two ventilatory modes (ATC vs. continuous positive airway pressure), three different sized endotracheal tubes (inner diameter 7.0, 8.0, and 9.0 mm), two ventilatory rates (15/min and 30/min), and four levels of positive end-expiratory pressure (0, 5, 10, and 15 cm H2O). Measurements and Main ResultsPerformance of tube compensation was assessed by the amount of tube-related (additional) work of breathing (WOBadd), which was calculated on the basis of pressure gradient across the endotracheal tube. Compared with continuous positive airway pressure, ATC reduced inspiratory WOBadd by 58%, 68%, 50%, and 97% when using the Evita 4, the Evita 2 prototype, the Puritan-Bennett 840, and the original ATC system, respectively. Depending on endotracheal tube diameter and ventilatory pattern, inspiratory WOBadd was 0.12–5.2 J/L with the original ATC system, 1.5–28.9 J/L with the Puritan-Bennett 840, 10.4–21.0 J/L with the Evita 2 prototype, and 10.1–36.1 J/L with the Evita 4 (difference between each ventilator at identical test situations, p < .025). Expiratory WOBadd was reduced by 5%, 26%, 1%, and 70% with the Evita 4, the Evita 2 prototype, the Puritan-Bennett 840, and the original ATC system, respectively. The expiratory WOBadd caused by an endotracheal tube of 7.0 mm inner diameter was 5.5–42.2 J/L at a low ventilatory rate and 19.6–82.3 J/L at a high ventilatory rate. It was lowest with the original ATC system and highest with the Evita 4 ventilator (p < .025). ConclusionsFlow-adapted tube compensation by the original ATC system significantly reduced tube-related inspiratory and expiratory work of breathing. The commercially available ATC modes investigated here may be adequate for inspiratory but probably not for expiratory tube compensation.

Estimating intratidal nonlinearity of respiratory system mechanics: a model study using the enhanced gliding-SLICE method

In the clinical situation and in most research work, the analysis of respiratory system mechanics is limited to the estimation of single-value compliances during static or quasi-static conditions. In contrast, our SLICE method analyses intratidal nonlinearity under the dynamic conditions of mechanical ventilation by calculating compliance and resistance for six conjoined volume portions (slices) of the pressure-volume loop by multiple linear regression analysis. With the gliding-SLICE method we present a new approach to determine continuous intratidal nonlinear compliance. The performance of the gliding-SLICE method was tested both in computer simulations and in a physical model of the lung, both simulating different intratidal compliance profiles. Compared to the original SLICE method, the gliding-SLICE method resulted in smaller errors when calculating the compliance or pressure course (all p < 0.001) and in a significant reduction of the discontinuity error for compliance determination which was reduced from 12.7 +/- 7.2 cmH(2)O s L(-1) to 0.8 +/- 0.3 cmH(2)O s L(-1) (mathematical model) and from 7.2 +/- 3.9 cmH(2)O s L(-1) to 0.4 +/- 0.2 cmH(2)O s L(-1) (physical model) (all p < 0.001). We conclude that the new gliding-SLICE method allows detailed assessment of intratidal nonlinear respiratory system mechanics without discontinuity error.

Detection of partial endotracheal tube obstruction by forced pressure oscillations

Rapid airway occlusions during mechanical ventilation are followed immediately by high-frequency pressure oscillations. To answer the question if the frequency of forced pressure oscillations is an indicator for partial obstruction of the endotracheal tube (ETT) we performed mathematical simulations and studies in a ventilated physical lung model. Model-derived predictions were evaluated in seven healthy volunteers. Partial ETT obstruction was mimicked by decreasing the inner diameter (ID) of the ETT. In the physical model ETTs of different ID were used. In spontaneously breathing volunteers viscous fluid was applied into the ETTs lumen. According to the predictions derived from mathematical simulations, narrowing of the ETTs ID from 9.0 to 7.0mm decreased the frequency of the pressure oscillations by 11% while changes of the respiratory systems compliance had no effect. In volunteers, a similar reduction (10.9%) was found when 5 ml fluid were applied. We conclude that analysis of pressure oscillations after flow interruption offers a tool for non-invasive detection of partial ETT obstruction.

Short-term effects of positive end-expiratory pressure on breathing pattern: an interventional study in adult intensive care patients

IntroductionPositive end-expiratory pressure (PEEP) is used in mechanically ventilated patients to increase pulmonary volume and improve gas exchange. However, in clinical practice and with respect to adult, ventilator-dependent patients, little is known about the short-term effects of PEEP on breathing patterns.MethodsIn 30 tracheally intubated, spontaneously breathing patients, we sequentially applied PEEP to the trachea at 0, 5 and 10 cmH2O, and then again at 5 cmH2O for 30 s each, using the automatic tube compensation mode.ResultsIncreases in PEEP were strongly associated with drops in minute ventilation (P < 0.0001) and respiratory rate (P < 0.0001). For respiratory rate, a 1 cmH2O change in PEEP in either direction resulted in a change in rate of 0.4 breaths/min. The effects were exclusively due to changes in expiratory time. Effects began to manifest during the first breath and became fully established in the second breath for each PEEP level. Identical responses were found when PEEP levels were applied for 10 or 60 s. Post hoc analysis revealed a similar but stronger response in patients with impaired respiratory system compliance.ConclusionIn tracheally intubated, spontaneously breathing adult patients, the level of PEEP significantly influences the resting short-term breathing pattern by selectively affecting expiratory time. These findings are best explained by the Hering–Breuer inflation/deflation reflex.

Effects of mechanical unloading/loading on respiratory loop gain and periodic breathing in man

We investigated the effect of mechanical unloading and loading on Cheyne-Stokes respiration (CSR) in seven intubated patients with preexisting CSR. For mechanical loading patients had to breathe against the resistance of the endotracheal tube. For mechanical unloading patients were supported with a volume-proportional pressure support in the proportional assist ventilation (PAV) mode whilst the flow-dependent (nonlinear) endotracheal tube resistance was continuously compensated for by means of the automatic tube compensation (ATC) mode. Mechanical unloading aggravated CSR as revealed by a prolongation of apnea time and by an increase in the so-called strength index whereas mechanical loading shortened apnea time and decreased strength index. To test whether the observed changes are caused by the effect of mechanical unloading/loading on respiratory loop gain (relationship between minute ventilation and arterial CO2 tension), the response of respiratory loop gain on mechanical unloading/loading was determined in five healthy subjects (without CSR). In each subject, mechanical unloading increased respiratory loop gain whereas mechanical loading decreased it.

Expiratory automatic endotracheal tube compensation reduces dynamic hyperinflation in a physical lung model

IntroductionThe effect of expiratory endotracheal tube (ETT) resistance on dynamic lung inflation is unknown. We hypothesized that ETT resistance causes dynamic lung hyperinflation by impeding lung emptying. We further hypothesized that compensation for expiratory ETT resistance by automatic tube compensation (ATC) attenuates dynamic lung hyperinflation.MethodsA ventilator equipped with the original ATC mode and operating in a pressure-targeted mode was connected to a physical lung model that consists of four equally sized glass bottles filled with copper wool. Inspiratory pressure, peak expiratory flow, trapped lung volume and intrinsic positive end-expiratory pressure (PEEP) were assessed at combinations of four inner ETT diameters (7.0, 7.5, 8.0 and 8.5 mm), four respiratory rates (15, 20, 25 and 30/minute), three inspiratory pressures (3.0, 4.5 and 6.0 cmH2O) and four lung compliances (113, 86, 58 and 28 ml/cmH2O). Intrinsic PEEP was measured at the end of an expiratory hold manoeuvre.ResultsAt a given test lung compliance, inspiratory pressure and ETT size, increasing respiratory rates from 15 to 30/minutes had the following effects: inspiratory tidal volume and peak expiratory flow were decreased by means of 25% (range 0% to 51%) and 11% (8% to 12%), respectively; and trapped lung volume and intrinsic PEEP were increased by means of 25% (0% to 51%) and 26% (5% to 45%), respectively (all P < 0.025). At otherwise identical baseline conditions, introduction of expiratory ATC significantly attenuated (P < 0.025), by approximately 50%, the respiratory rate-dependent decreases in inspiratory tidal volume and the increases in trapped lung volume and intrinsic PEEP.ConclusionsIn a lung model of pressure-targeted ventilation, expiratory ETT resistance caused dynamic lung hyperinflation during increases in respiratory rates, thereby reducing inspiratory tidal volume. Expiratory ATC attenuated these adverse effects.

Breathing pattern and perception at different levels of volume assist and pressure support in volunteers

ObjectiveVolume assist (VA) amplifies the breathing effort whereas pressure support ventilation (PSV) provides a fixed, effort-independent ventilatory support. According to the concept of VA, its level should compensate for the pathologically increased (additional) elastance (Eadd). However, it is unclear whether breathing subjects prefer an exact compensation of Eadd and whether they are able to adjust the support level by themselves. DesignProspective, interventional study. SettingLaboratory. SubjectsTwelve healthy volunteers, nine females, three males, aged 21–33 yrs. InterventionsIncreased Eadd was generated by banding of the thorax and abdomen. Volunteers breathed via a mouthpiece with VA or PSV using a positive end-expiratory pressure of 5 cm H2O (0.5 kPa). The study was subdivided into two parts. In part I, volunteers were instructed to adjust the level of VA and PSV themselves starting from three different, randomly applied levels in each mode (2, 8, 14 cm H2O or cm H2O/L; 0.2, 0.8, 1.4 kPa[/L]). In part II, 20 levels of VA and PSV (1–20 cm H2O or cm H2O/L, 0.1–2 kPa[/L]) were randomly selected by an investigator and estimated by the volunteers using a visual analog scale. Additionally, the breathing pattern was characterized. Measurements and Main Results Eadd (7.1 ± 1.5 cm H2O/L [0.7 ± 0.2 kPa/L], mean ± sd) corresponded almost exactly to the “self-adjusted” VA level of part I (7.0 ± 3.3 cm H2O/L [0.7 ± 0.3 kPa/L]) and to the adequate level of part II (8–9 cm H2O/L [0.8–0.9 kPa/L]). The accordant PSV levels were 5.7 ± 2.6 cm H2O (0.6 ± 0.3 kPa) and 6–7 cm H2O (0.6–0.7 kPa). The breathing pattern was less influenced by changes of the support level with VA compared with PSV, which may explain in part the greater comfort of VA. ConclusionsWe confirmed the theoretical assumption that VA should be adapted to Eadd. Furthermore, we demonstrated that conscious subjects are able to adjust the level of VA and PSV themselves.

Acute respiratory distress syndrome: rather a (vague) concept than a (clear) definition*.

www.ccmjournal.org 2055 Acute respiratory distress syndrome (ARDS) complicates many severe medical and surgical conditions. Following its initial description in 1967 (1), we have learned tremendously about its pathophysiology, diagnosis, and treatment. In addition, the definition of ARDS has been repeatedly refined (2, 3). Despite our growing knowledge, the question whether ARDS is a true disease entity or rather a condition resulting from various impacts is not settled (3). Severe impairment of pulmonary gas exchange—not necessarily identical to ARDS—is well known and dreaded in severe neurologic injury (e.g., [4]) and may contribute to high mortality in these patients. In this issue of Critical Care Medicine, Elmer et al (5) from Pittsburgh and Boston report the prevalence of “ARDS” in a large cohort of patients with spontaneous intracerebral hemorrhage. In 27% of their patients, ARDS was diagnosed as a complicating condition. Their report is meticulous and interesting to read. However, interpretation of their findings is less straightforward than expected on first sight. First, the high prevalence of 27% is astonishing, albeit comparable prevalences of ARDS have been observed by others in patients with similar severe neurologic sequelae (e.g., [6]). The prevalence may even have been underestimated because not all patients received diagnostic measures like arterial blood gas analysis and chest radiograph due to futility and other considerations of the attending physician. As a second point of interest, ARDS was observed rather early during the course of the treatment, predominantly on day 1 or 2. Among others, a high tidal volume was found to be an independent risk factor for the development of ARDS, as well as for inhospital mortality. Astonishingly, a potential influence of the level of positive end-expiratory pressure (PEEP)—presumably rather low with respect to intracranial pressure—was not studied, albeit PEEP has been recorded. PEEP was only considered in the diagnosis of ARDS following the actual Berlin definition (3). Most astonishingly, the occurrence of ARDS did not influence the rather poor prognosis of the patients studied. As speculated by the authors, a potential influence of ARDS on survival may have been obscured by the high mortality caused by intracranial hemorrhage itself. In contrast, survival was significantly deteriorated by high tidal volume ventilation. However, when considering the remarks above all together, one may ask whether the authors observed “true” ARDS or rather neurogenic pulmonary edema in their patients. Neurogenic pulmonary edema is a well-known disease entity for those of us treating patients with all kinds of severe neurologic sequelae (7). Impairment of gas exchange is sometimes severe and even life threatening. However, the course of neurogenic pulmonary edema is usually benign and its resolution is rapid (8). In contrast, true ARDS is a condition lasting for several days if not weeks. It is an ongoing threat for the patients’ life. Differences between ARDS and neurogenic pulmonary edema are explained by pathophysiology. In ARDS, inflammation is a key component of the disease process (9–11), whereas in neurogenic pulmonary edema, inflammation is not involved (12). Vascular and cardial components are predominating instead (7). When considering the actual (3) and the previous (2) definitions of ARDS, such differentiation is not undertaken. ARDS is diagnosed based on certain criteria for pulmonary gas exchange, bilateral infiltrates on chest radiographs, absence of cardial origin of edema, and acuteness of the condition. It is bound to a catastrophic event or acute severe deterioration of health. So, the definition is rather unspecific aiming on feasibility. However, Ashbaughs et al’s description (1) and the understanding of the ARDS Definition Task Force is that “... ARDS is a type of acute diffuse, inflammatory lung injury ...” (3) corresponding well to the clinical understanding of most “ARDSologists” at the bedside. So, we would strongly vote to reserve the term ARDS for conditions with compatible pathophysiology, that is, inflammation as a key driver of lung injury. Notwithstanding, the findings of Elmer et al (5) are important and definitively worth reading. Their vote for reducing tidal volume in this population should be strongly considered. Current evidence (weakly) supports such consideration when initiating mechanical ventilation in general (13). Nevertheless, inappropriate use of the term ARDS should be avoided. However, from a patient’s perspective, terminology is irrelevant but appropriate treatment. From this point of view, the study by Elmer et al (5) is important and rightful. Copyright