Lothar A. Schwarte

Monitoring tissue oxygenation by near infrared spectroscopy (NIRS): background and current applications.

Conventional cardiovascular monitoring may not detect tissue hypoxia, and conventional cardiovascular support aiming at global hemodynamics may not restore tissue oxygenation. NIRS offers non-invasive online monitoring of tissue oxygenation in a wide range of clinical scenarios. NIRS monitoring is commonly used to measure cerebral oxygenation (rSO2), e.g. during cardiac surgery. In this review, we will show that tissue hypoxia occurs frequently in the perioperative setting, particularly in cardiac surgery. Therefore, measuring and obtaining adequate tissue oxygenation may prevent (postoperative) complications and may thus be cost-effective. NIRS monitoring may also be used to detect tissue hypoxia in (prehospital) emergency settings, where it has prognostic significance and enables monitoring of therapeutic interventions, particularly in patients with trauma. However, optimal therapeutic agents and strategies for augmenting tissue oxygenation have yet to be determined.

Levosimendan is superior to milrinone and dobutamine in selectively increasing microvascular gastric mucosal oxygenation in dogs.

Objective:The effect of levosimendan, a novel inotropic vasodilator (inodilator), on the microvascular gastric mucosal hemoglobin oxygenation (&mgr;Hbo2) is unknown. A possible effect could thereby be selective for the splanchnic region or could primarily reflect changes in systemic oxygen transport (&U1E0A;o2) and/or oxygen consumption (&OV0312;o2). We compared systemic and regional effects of levosimendan with those of established inotropes, milrinone and dobutamine. Design:Laboratory experiment. Setting:University animal research laboratory of experimental anesthesiology. Subjects:Chronically instrumented dogs with flow probes for cardiac output measurement. Interventions:Anesthetized, mechanically ventilated dogs (each group n = 6) on different days randomly received levosimendan (10 &mgr;g·kg−1, followed by four infusion steps: 0.125–1.0 &mgr;g·kg−1·min−1), milrinone (5.0 &mgr;g·kg−1, followed by 1.25–10 &mgr;g·kg−1·min−1), or dobutamine (2.5–10.0 &mgr;g·kg−1·min−1). Since these drugs may modify regional or systemic responses to fluid load, an additional predefined volume challenge was subsequently performed with hydroxyethyl starch 6% (10 mL·kg−1). Measurements and Main Results:We measured &mgr;Hbo2 (reflectance spectrophotometry), &U1E0A;o2, &OV0312;o2, and systemic hemodynamics. Levosimendan significantly increased &mgr;Hbo2 from baseline (∼55% for all groups) to 64 ± 4% and further to 69 ± 2% with volume challenge (mean ± sem). At the systemic level, levosimendan alone only slightly increased &U1E0A;o2 at a stable &OV0312;o2. Milrinone elicited similar systemic effects (&U1E0A;o2, &OV0312;o2, hemodynamics) but failed to increase &mgr;Hbo2. Dobutamine, conversely, increased &mgr;Hbo2 to a similar extent as levosimendan; however, this was accompanied by marked increases in &U1E0A;o2 and &OV0312;o2. The gastric mucosa selectivity of these interventions, expressed as slope of the &mgr;Hbo2/&U1E0A;o2 relation, was highest for levosimendan (+1.89 and +1.14, without and with volume challenge), compared with milrinone (+0.45 and + 0.47) and dobutamine (+0.48 and + 0.33). Conclusions:Levosimendan is superior to milrinone (no significant regional effects) and dobutamine (marked systemic effects) in increasing gastric mucosal oxygenation selectively (i.e., at only moderately increased &U1E0A;o2 and stable &OV0312;o2). If our experimental data apply to the clinical setting, levosimendan may serve as an option to selectively increase gastrointestinal mucosa oxygenation in patients at risk to develop splanchnic ischemia.

Perioperative Hemodynamic Monitoring with Transesophageal Doppler Technology

Invasive cardiac output (CO) monitoring, traditionally performed with transpulmonary thermodilution techniques, is usually reserved for high-risk patients because of the inherent risks of these methods. In contrast, transesophageal Doppler (TED) technology offers a safe, quick, and less invasive method for routine measurements of CO. After esophageal insertion and focusing of the probe, the Doppler beam interrogates the descending aortic blood flow. On the basis of the measured frequency shift between the emitted and received ultrasound frequency, blood flow velocity is determined. From this velocity, combined with the simultaneously measured systolic ejection time, CO and other advanced hemodynamic variables can be calculated, including estimations of preload, afterload, and contractility. Numerous studies have validated TED-derived CO against reference methods. Although the agreement of CO values between TED and the reference methods is limited (95% limits of agreement: median 4.2 L/min, interquartile range 3.3–5.0 L/min), TED has been shown to accurately follow changes of CO over time, making it a useful device for trend monitoring. TED can be used to guide perioperative intravascular volume substitution and therapy, with vasoactive or inotropic drugs. Various studies have demonstrated a reduced postoperative morbidity and shorter length of hospital stay in patients managed with TED compared with conventional clinical management, suggesting that it may be a valuable supplement to standard perioperative monitoring. We review not only the technical basis of this method and its clinical application but also its limitations, risks, and contraindications.

Peep Decreases Oxygenation of the Intestinal Mucosa Despite Normalization of Cardiac Output

OBJECTIVE To evaluate if normalization of cardiac output reverses the attenuation of local intracapillary hemoglobin saturation (HbO2) of gastric mucosa by PEEP (positive end-expiratory pressure) during IPPV (intermittent positive pressure ventilation). MATERIALS AND METHODS Four healthy, chronically instrumented, anesthetized dogs were repeatedly studied (n = 7). Local HbO2 of gastric mucosa was measured continuously by tissue lightguide spectrophotometry and cardiac output (CO) was recorded continuously by means of a precalibrated ultrasonic transit time flowmeter chronically implanted around the pulmonary artery. After obtaining baseline values during IPPV and ZEEP (zero end-expiratory pressure) 15 cmH2O PEEP was added. To compensate the reduction of CO during PEEP ventilation, HES (hydroxyethyl starch 6%) was infused until CO reached baseline values during ZEEP. RESULTS Despite of unimpaired systemic oxygen saturation, PEEP reduced HbO2 of gastric mucosa from 55.1 +/- 4.2% to 42.1 +/- 4.7% (mean +/- SEM) and CO dropped from 67.7 +/- 4.9 ml.kg-1.min-1 to 33.9 +/- 4.6 ml.kg-1.min-1. Whereas infusion of HES during PEEP ventilation normalized CO to 65.1 +/- 6.2 ml.kg-1.min-1, HbO2 reached only 48.1 +/- 3.3%, a statistically significant improvement compared to HbO2 during PEEP ventilation before HES infusion (p < 0.03, Wilcoxon signed rank test), but still below baseline values (p < 0.04). CONCLUSIONS Our findings demonstrate that the side effects of PEEP ventilation on cardiac output can be compensated by restoring preload, but normalizing CO did not completely normalize HbO2 of the gastric mucosa. This further emphasizes that global measurements of variables of systemic circulation and oxygenation do not necessarily reflect regional abnormalities of tissue oxygenation. Therefore, in view of the importance of tissue hypoxia especially in the splanchnic region in the pathogenesis of multiple organ failure, monitoring of HbO2 of the intestinal mucosa during PEEP ventilation may be particularly useful in the care of the critically ill patient.

Moderate Increase in Intraabdominal Pressure Attenuates Gastric Mucosal Oxygen Saturation in Patients Undergoing Laparoscopy

Background: Perioperative disturbances of microvascular blood flow and oxygenation in the intestinal tract have been hypothesized to play an important role in development of the multiple organ dysfunction syndrome. Herein, increased intra-abdominal pressure (IAP) has been identified as a key factor in the initiation of the pathophysiologic cascade. The authors hypothesized that increasing the IAP by intraperitoneal insufflation of carbon dioxide attenuates microvascular oxygen saturation in gastric mucosa. They tested this hypothesis in a prospective, observational study in 16 patients scheduled to undergo elective diagnostic laparoscopy. Methods: The authors continuously assessed microvascular oxygen saturation in gastric mucosa by reflectance spectrophotometry. Simultaneously systemic oxygen saturation, heart rate, arterial blood pressure, and ventilation-derived variables were measured noninvasively. During general anesthesia and controlled mechanical ventilation, baseline values were obtained. Thereafter, the IAP was increased to 8 and 12 mmHg, respectively, followed by a control period after desufflation. Results: The increase in IAP from baseline to 8 mmHg decreased microvascular oxygen saturation in gastric mucosa from 69 ± 7% (mean ± SD) to 63 ± 8% at 8 mmHg IAP (P <0.05), with a further significant reduction to 54 ± 13% at 12 mmHg IAP (P <0.01). Microvascular oxygen saturation in gastric mucosa recovered rapidly to baseline level (66 ± 10%) after release of increased IAP. In striking contrast to regional mucosal oxygen saturation, systemic oxygenation did not change with either of the interventions. Conclusions: The results suggest that increasing intraabdominal pressure to moderate levels, commonly applied to induce a surgical pneumoperitoneum, decreases gastric mucosal oxygen saturation.

Distinct alterations in sublingual microcirculatory blood flow and hemoglobin oxygenation in on-pump and off-pump coronary artery bypass graft surgery

OBJECTIVE The authors hypothesized that cardiopulmonary bypass (CPB) (on-pump) is associated with more severe changes in the microcirculatory blood flow and tissue oxygenation as compared with off-pump coronary artery bypass surgery. DESIGN An observational study. SETTING A university hospital and teaching hospital. PARTICIPANTS Patients undergoing on-pump (n = 24) or off-pump (n = 24) cardiac surgery. INTERVENTIONS Microcirculatory measurements were performed before CPB and 10 minutes after the switch to CPB or before and during cardiac luxation in off-pump patients. MEASUREMENTS AND MAIN RESULTS Sublingual microcirculatory perfusion was investigated using side-stream dark field imaging, and sublingual microcirculatory oxygenation was measured using reflectance spectrophotometry. Conversion to CPB resulted in an increase in cardiac output from 4.0 ± 0.2 to 4.8 ± 0.3 L/min (p < 0.01) and a 40% reduction in arterial hemoglobin concentration. Cardiopulmonary bypass was associated with an increase in venular blood velocity from 349 ± 201 μm/s to 563 ± 227 μm/s (p < 0.05), a reduction in functional capillary density of 43%, and an increase in hemoglobin oxygenation of the red blood cells in the remaining filled capillaries from 47.2% ± 6.1% to 59.7% ± 5.2% (p < 0.001). The decrease in cardiac output during cardiac luxation from 4.5 ± 1.7 to 1.8 ± 0.8 L/min (p < 0.01) without hemoglobin changes was associated with a complete halt of capillary blood flow and a reduction in maximum capillary blood velocity from 895 ± 209 to 396 ± 178 μm/s (p < 0.01). The functional capillary density remained unchanged, whereas the hemoglobin oxygenation declined from 64.2% ± 9.1% to 48.6% ± 8.7% (p < 0.01). CONCLUSIONS On-pump and off-pump cardiac surgery are associated with distinct alterations in sublingual microcirculatory perfusion and hemoglobin oxygenation. Although on-pump surgery results in a fall out of capillaries resulting in decreased oxygen extraction, off-pump surgery results in a cessation of flow during luxation resulting in decreased convection of oxygen transport.

The NO donor SIN-1 improves intestinal-arterial Pco2 gap in experimental endotoxemia: An animal study

Background:  Dysfunction of the microcirculation is a prominent feature of sepsis and endotoxemia. Recently, it has been shown that microcirculatory alterations are completely reversed by local or systemic application of vasodilators in severely septic patients. Therefore, we investigated the influence of vasodilator therapy on microcirculatory dysfunction of the ileum during endotoxic shock in a prospective, controlled animal study.

Experience in Prehospital Endotracheal Intubation Significantly Influences Mortality of Patients with Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Background Patients with severe traumatic brain injury (TBI) are at high risk for airway obstruction and hypoxia at the accident scene, and routine prehospital endotracheal intubation has been widely advocated. However, the effects on outcome are unclear. We therefore aim to determine effects of prehospital intubation on mortality and hypothesize that such effects may depend on the emergency medical service providers’ skill and experience in performing this intervention. Methods and Findings PubMed, Embase and Web of Science were searched without restrictions up to July 2015. Studies comparing effects of prehospital intubation versus non-invasive airway management on mortality in non-paediatric patients with severe TBI were selected for the systematic review. Results were pooled across a subset of studies that met predefined quality criteria. Random effects meta-analysis, stratified by experience, was used to obtain pooled estimates of the effect of prehospital intubation on mortality. Meta-regression was used to formally assess differences between experience groups. Mortality was the main outcome measure, and odds ratios refer to the odds of mortality in patients undergoing prehospital intubation versus odds of mortality in patients who are not intubated in the field. The study was registered at the International Prospective Register of Systematic Reviews (PROSPERO) with number CRD42014015506. The search provided 733 studies, of which 6 studies including data from 4772 patients met inclusion and quality criteria for the meta-analysis. Prehospital intubation by providers with limited experience was associated with an approximately twofold increase in the odds of mortality (OR 2.33, 95% CI 1.61 to 3.38, p<0.001). In contrast, there was no evidence for higher mortality in patients who were intubated by providers with extended level of training (OR 0.75, 95% CI 0.52 to 1.08, p = 0.126). Meta-regression confirmed that experience is a significant predictor of mortality (p = 0.009). Conclusions Effects of prehospital endotracheal intubation depend on the experience of prehospital healthcare providers. Intubation by paramedics who are not well skilled to do so markedly increases mortality, suggesting that routine prehospital intubation of TBI patients should be abandoned in emergency medical services in which providers do not have ample training, skill and experience in performing this intervention.

Assessment of microvascular oxygen saturation in gastric mucosa in volunteers breathing continuous positive airway pressure

OBJECTIVE Adequate oxygenation of the gastrointestinal mucosa to preserve its barrier function is a basic objective in the prevention of multiple organ failure. Sustaining a positive airway pressure during the entire respiratory cycle remains a cornerstone in the therapeutic regimen to improve systemic oxygenation. Whereas increased systemic oxygenation during breathing continuous positive airway pressure has been shown, the impact of continuous positive airway pressure on regional oxygenation in the gastrointestinal tract has not yet been evaluated. We hypothesized that continuous positive airway pressure decreases microvascular oxygen saturation in gastric mucosa. DESIGN Prospective, randomized study. SETTING University department of anesthesiology. PARTICIPANTS Twelve healthy volunteers. INTERVENTIONS Incremental increases of continuous positive airway pressure (0, 5, and 10 cm H(2)O) and subsequent release of continuous positive airway pressure. MEASUREMENTS AND MAIN RESULTS We continuously measured microvascular oxygen saturation in gastric mucosa by reflectance spectrophotometry. Systemic oxygen saturation, end-tidal Pco(2), respiratory rate, heart rate, and arterial blood pressure were obtained noninvasively. In every volunteer, microvascular oxygen saturation in gastric mucosa was reduced corresponding to the level of continuous positive airway pressure, although systemic variables, especially systemic oxygen saturation, did not change. Continuous positive airway pressure reduced microvascular oxygen saturation in gastric mucosa from 59 +/- 7% (baseline with 0 cm H(2)O continuous positive airway pressure, mean +/- sd) to 54 +/- 8% (p <.05) during 5 cm H(2)O continuous positive airway pressure and to 50 +/- 9% (p <.05) during 10 cm H(2)O continuous positive airway pressure, returning to 59 +/- 7% during spontaneous breathing with 0 cm H(2)O continuous positive airway pressure. End-tidal Pco(2), respiratory rate, as well as hemodynamic variables, remained stable. CONCLUSIONS Reflectance spectrophotometry meticulously monitored changes in microvascular oxygen saturation in gastric mucosa during breathing continuous positive airway pressure. Microvascular oxygen saturation in gastric mucosa decreased with increasing levels of continuous positive airway pressure despite steady systemic variables. These results suggest that the impact of altering airway pressures on splanchnic oxygenation is not mirrored necessarily by concomitant changes in systemic circulation. Moreover, if these findings also apply to critically ill patients, monitoring microvascular oxygen saturation in gastric mucosa would be useful to further optimize the setting of ventilation variables.

Dopexamine but not dopamine increases gastric mucosal oxygenation during mechanical ventilation in dogs

Objective To compare the effects of dopamine and dopexamine on gastric mucosal oxygenation during mechanical ventilation without and with positive end-expiratory airway pressure (PEEP) and after compensation of the PEEP-induced hemodynamic suppression. Design Randomized controlled animal study. Setting University research department of experimental anesthesiology. Subjects Ten anesthetized dogs with chronically implanted ultrasound flow probes around the pulmonary artery for continuous measurement of cardiac output. Interventions On different days, the dogs randomly received dopamine (2.5 and 5.0 &mgr;g·kg−1·min−1, n = 10), dopexamine (0.5 and 1.0 &mgr;g·kg−1·min−1) without (n = 8) or with pretreatment with a selective &bgr;2-adrenoceptor antagonist (ICI 118,551, n = 7), or saline (control, n = 7). To simulate common clinical situations, these interventions were performed during different ventilation modes: during mechanical ventilation without and with high levels of PEEP, and after compensation of the PEEP-induced systemic hemodynamic suppression by titrated volume resuscitation with hydroxyethyl starch. Measurements and Main Results We continuously measured microvascular hemoglobin saturation (&mgr;Hbo2) by light-guide spectrophotometry in the gastric mucosa. Dopexamine, but not dopamine, significantly increased gastric mucosal &mgr;Hbo2 by about 20%, regardless of the dose and the ventilation mode. Both catecholamines dose-dependently increased cardiac output and oxygen delivery by up to 75% without effects on systemic oxygen saturation. The effects of dopexamine on &mgr;Hbo2 as well as on cardiac output and oxygen delivery were prevented by selective &bgr;2-adrenoceptor-blockade. Conclusions Dopexamine but not dopamine improved gastric mucosal oxygenation in dogs. This effect was independent of the dosage and the ventilation mode. Thus, dopexamine may reverse a decrease in splanchnic oxygenation induced by ventilation with PEEP. The dopexamine-induced increase in gastric mucosal oxygenation was mediated by &bgr;2-adrenoceptors, which explains the superior effects of dopexamine to dopamine on &mgr;Hbo2. The regional effects of both catecholamines were not mirrored by systemic hemodynamics.