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Objectives: We developed quantitative methods to analyze microbubble kinetics based on renal contrast-enhanced ultrasound imaging combined with measurements of sublingual microcirculation on a fixed area to quantify early microvascular alterations in sepsis-induced acute kidney injury. Design: Prospective controlled animal experiment study. Setting: Hospital-affiliated animal research institution. Subjects: Fifteen female pigs. Interventions: The animals were instrumented with a renal artery flow probe after surgically exposing the kidney. Nine animals were given IV infusion of lipopolysaccharide to induce septic shock, and six were used as controls. Measurements and Main Results: Contrast-enhanced ultrasound imaging was performed on the kidney before, during, and after having induced shock. Sublingual microcirculation was measured continuously using the Cytocam on the same spot. Contrast-enhanced ultrasound effectively allowed us to develop new analytical methods to measure dynamic variations in renal microvascular perfusion during shock and resuscitation. Renal microvascular hypoperfusion was quantified by decreased peak enhancement and an increased ratio of the final plateau intensity to peak enhancement. Reduced intrarenal blood flow could be estimated by measuring the microbubble transit times between the interlobar arteries and capillary vessels in the renal cortex. Sublingual microcirculation measured using the Cytocam in a fixed area showed decreased functional capillary density associated with plugged sublingual capillary vessels that persisted during and after fluid resuscitation. Conclusions: In our lipopolysaccharide model, with resuscitation targeted at blood pressure, contrast-enhanced ultrasound imaging can identify renal microvascular alterations by showing prolonged contrast enhancement in microcirculation during shock, worsened by resuscitation with fluids. Concomitant analysis of sublingual microcirculation mirrored those observed in the renal microcirculation.

Supplemental Digital Content is available in the text., OBJECTIVES: In this study, we hypothesized that coronavirus disease 2019 patients exhibit sublingual microcirculatory alterations caused by inflammation, coagulopathy, and hypoxemia. DESIGN: Multicenter case-controlled study. SETTING: Two ICUs in The Netherlands and one in Switzerland. PATIENTS: Thirty-four critically ill coronavirus disease 2019 patients were compared with 33 healthy volunteers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The microcirculatory parameters quantified included total vessel density (mm × mm–2), functional capillary density (mm × mm–2), proportion of perfused vessels (%), capillary hematocrit (%), the ratio of capillary hematocrit to systemic hematocrit, and capillary RBC velocity (μm × s–1). The number of leukocytes in capillary-postcapillary venule units per 4-second image sequence (4 s–1) and capillary RBC microaggregates (4 s–1) was measured. In comparison with healthy volunteers, the microcirculation of coronavirus disease 2019 patients showed increases in total vessel density (22.8 ± sd 5.1 vs 19.9 ± 3.3; p < 0.0001) and functional capillary density (22.2 ± 4.8 vs 18.8 ± 3.1; p < 0.002), proportion of perfused vessel (97.6 ± 2.1 vs 94.6 ± 6.5; p < 0.01), RBC velocity (362 ± 48 vs 306 ± 53; p < 0.0001), capillary hematocrit (5.3 ± 1.3 vs 4.7 ± 0.8; p < 0.01), and capillary-hematocrit-to-systemic-hematocrit ratio (0.18 ± 0.0 vs 0.11 ± 0.0; p < 0.0001). These effects were present in coronavirus disease 2019 patients with Sequential Organ Failure Assessment scores less than 10 but not in patients with Sequential Organ Failure Assessment scores greater than or equal to 10. The numbers of leukocytes (17.6 ± 6.7 vs 5.2 ± 2.3; p < 0.0001) and RBC microaggregates (0.90 ± 1.12 vs 0.06 ± 0.24; p < 0.0001) was higher in the microcirculation of the coronavirus disease 2019 patients. Receiver-operating-characteristics analysis of the microcirculatory parameters identified the number of microcirculatory leukocytes and the capillary-hematocrit-to-systemic-hematocrit ratio as the most sensitive parameters distinguishing coronavirus disease 2019 patients from healthy volunteers. CONCLUSIONS: The response of the microcirculation to coronavirus disease 2019-induced hypoxemia seems to be to increase its oxygen-extraction capacity by increasing RBC availability. Inflammation and hypercoagulation are apparent in the microcirculation by increased numbers of leukocytes and RBC microaggregates.

Objectives: Reliable automated handheld vital microscopy image sequence analysis and the identification of disease states and effects of therapy are prerequisites for the routine use of quantitative sublingual microcirculation measurements at the point-of-care. The present study aimed to clinically validate the recently introduced MicroTools software in a large multicentral database of perioperative and critically ill patients and to use this automatic algorithm to data-mine and identify the sublingual microcirculatory variable changes in response to disease and therapy. Design: Retrospective algorithm-based image analysis and data-mining within a large international database of sublingual capillary microscopy. Algorithm-based analysis was compared with manual analysis for validation. Thereafter, MicroTools was used to identify the functional microcirculatory alterations associated with disease conditions and identify therapeutic options for recruiting functional microcirculatory variables. Setting: Ten perioperative/ICU/volunteer studies in six international teaching hospitals. Patients: The database encompass 267 adult and pediatric patients undergoing surgery, treatment for sepsis, and heart failure in the ICU and healthy volunteers. Interventions: Perioperative and ICU standard of care. Measurements and Main Results: One thousand five hundred twenty-five handheld vital microscopy image sequences containing 149,257 microscopy images were analyzed. 3.89 × 1012 RBC positions were tracked by the algorithm in real time, and offline manual analysis was performed. Good correlation and trending ability were found between manual and automatic total and functional capillary density (r = 0.6–0.8; p < 0.0001). RBC tracking within the database demonstrated changes in functional capillary density and/or RBC velocity in septic shock, heart failure, hypovolemia, obstructive shock, and hemodilution and thus detected the presence of a disease condition. Therapies recruiting the microcirculatory diffusion and convection capacity associated with systemic vasodilation and an increase in cardiac output were separately identified. Conclusions: Algorithm-based analysis of the sublingual microcirculation closely matched manual analysis across a broad spectrum of populations. It successfully identified a methodology to quantify microcirculatory alterations associated with disease and the success of capillary recruitment, improving point-of-care application of microcirculatory-targeted resuscitation procedures.

Objectives: Most knowledge related to the pathophysiology of microcirculation in ischemic stroke comes from experimental research. Unfortunately, data on microcirculation in the human brain are limited, partially as a result of the lack of appropriate investigational techniques. The objective of our study was to test the hypothesis that cortical microcirculatory alterations in the brain, in terms of blood flow and vessel density, occur in patients with stroke who require surgical decompression compared with a control group. Design: Prospective and observational study. Setting: Third-level university hospital. Patients: Six patients who had undergone decompressive surgery as a result of a space-occupying hemispheric infarction. These patients were compared with five patients who had undergone craniotomy for a disease not affecting the cortex. Interventions: Cortical microcirculation in the brain was directly observed using sidestream dark-field imaging. All images were analyzed offline. Measurements and Main Results: In patients with stroke with a space-occupying hemispheric infarction, 18 good-quality movie images were compared with 25 control group images. In the control group, cortical vessels showed a continuous flow in small, medium, and large vessels compared with patients with stroke who presented intermittent or no flow in all vessels. The proportion of perfused vessels was near 100% in control subjects and 63.44% in patients with stroke. The perfused vessel density index was also higher in control subjects (6.16 1/mm; interquartile range, 5.65-7.56) than in patients with stroke (2.77 1/mm; interquartile range, 1.75-3.86). Conclusion: Sidestream dark-field imaging allowed direct visualization of cerebral microcirculatory alterations in the operating room. This technique allowed the documentation of a significant blood flow reduction in the cortical microvascular and a decreased vascular density in patients with stroke compared with control subjects. (Crit Care Med 2011; 39:1126-1129)

Objective: The behavior of the human microcirculation in the setting of cardiac arrest is largely unknown. Animal experiments have consistently revealed that global hemodynamics do not necessarily reflect microvascular perfusion. In addition, the time it takes for capillary blood flow to stop after the heart arrests is debated. Estimations range from 50 seconds to 5 mins, but data in humans are lacking. Aortic arch surgery frequently necessitates deep hypothermic circulatory arrest and subsequent selective antegrade cerebral perfusion. To elucidate microvascular behavior surrounding cessation of human circulation, we used sublingual microvascular imaging in this setting. Design: Prospective, observational study. Setting: Operating room of a large tertiary referral center for cardiac surgery. Patients: Seven patients undergoing elective aortic arch repair. Interventions: We used sidestream dark field imaging to study the sublingual microcirculation immediately before circulatory arrest, during circulatory arrest, and immediately after selective antegrade cerebral perfusion. Measurements and Main Results: Results are reported as mean (SD) unless indicated otherwise. Before circulatory arrest, perfused vessel density was 6.41 (1.18) for small ( 20 mu m) microvessels. Microvascular flow index was a median of 3.0 (interquartile range 3.0-3.0) for both vessel sizes. After circulatory arrest, there was no equilibration of arterial and venous blood pressure before onset of selective antegrade cerebral perfusion after 59 (17) secs (range, 40-80 secs). Flow in small microvessels came to a complete stop after 45 (9) secs (range, 34-57 secs) after transition to circulatory arrest. However, flow in larger microvessels did not completely stop before selective antegrade cerebral perfusion started. Selective antegrade cerebral perfusion restored microvascular flow, reaching precirculatory arrest levels after 45 (27) secs (range, 20-85 secs). Conclusions: In a controlled surgical setting, circulatory arrest in humans induces a complete sublingual small microvessel shutdown within 1 min. However, flow in larger microvessels persists. Selective antegrade cerebral perfusion was able to restore microvascular flow to precirculatory arrest levels within a similar timeframe. (Crit Care Med 2010; 38:1548-1553)

To determine the impact of brief periods of cardiac arrest (CA) on regional cerebral oxygen saturation (rSO2) in patients with low left ventricular ejection fraction (LVEF30%).Prospective observational study.Cardiac surgery room at a university hospital.Seventy-seven consecutive patients undergoing elective implantation of a cardioverter/defibrillator in monitored anesthesia care. According to preoperative assessments, left ventricular function was classified as normal (LVEF50%), moderately impaired (LVEF 30%-50%), or severely reduced (LVEF30%).None.rSO2 was determined during threshold testing with concomitant induction of CA. In patients with LVEF30%, mean baseline rSO2 (59%) was already below the lower range of normal despite normal arterial blood pressure, heart rate, and arterial oxygen saturation. rSO2 increased by 6% after 6 L/min oxygen insufflation (p0.05) and dropped again in each group after CA, reaching a nadir after successful defibrillation. Patients with LVEF30% and baseline rSO263% exhibited the lowest values. They also showed the highest incidence (11%) of critical cerebral desaturations (i.e.,20% drop from baseline or rSO2 value50%). rSO2 in patients with LVEF30% was always below that determined in patients with LVEF30% (p0.05). There was a strong correlation between rSO2 values before CA and rSO2 nadir (p0.05). The drop in rSO2 was only moderately related to the brief CAs (p0.05).These findings demonstrate that severely compromised left ventricular pump function is associated with diminished rSO2. As these patients seem to be more susceptible to critical desaturations, they may be prone to severe tissue hypoxemia unless adequate oxygen delivery is reestablished rapidly. This may contribute to the poor neurologic outcome after successful resuscitation in patients with LVEF30%.

Objective: The physical examination of peripheral perfusion based on touching the skin or measuring capillary refill time has been related to the prognosis of patients with circulatory shock. It is unclear, however, whether monitoring peripheral perfusion after initial resuscitation still provides information on morbidity in critically ill patients. Therefore, we investigated whether subjective assessment of peripheral perfusion could help identify critically ill patients with a more severe organ or metabolic dysfunction using the Sequential Organ Failure Assessment (SOFA) score and lactate levels. Design: Prospective observational study. Setting. Multidisciplinary intensive care unit in a university hospital. Patients: Fifty consecutive adult patients admitted to the intensive care unit. Interventions. None. Measurements and Main Results., Patients were considered to have abnormal peripheral perfusion if the examined extremity had an increase in capillary refill time (>4.5 seconds) or it was cool to the examiner hands. To address reliability of subjective inspection and palpation of peripheral perfusion, we also measured forearm-to-fingertip skin-temperature gradient (Tskin-diff), central-to-toe temperature difference (Tc-toe), and peripheral flow index. The measurements were taken within 24 hours of admission to the intensive care after hemodynamic stability was obtained (mean arterial pressure >65 mm Hg). Changes in SOFA score during the first 48 hours were analyzed (delta-SOFA). Individual SOFA score was significantly higher in patients with abnormal peripheral perfusion than in those with normal peripheral perfusion (9 +/- 3 vs. 7 +/- 2, p < 0.05). Tskin-diff, Tc-toe, and peripheral flow index were congruent with the subjective assessment of peripheral perfusion. The proportion of patients with delta-SOFA score >0 was significantly higher in patients with abnormal peripheral perfusion (77% vs. 23%, p < 0.05). The logistic regression analysis showed that the odds of unfavorable evolution are 7.4 (95% confidence interval 2-19; p < 0.05) times higher for a patient with abnormal peripheral perfusion. The proportion of hyperlactatemia was significantly different between patients with abnormal and normal peripheral perfusion (67% vs. 33%, p < 0.05). The odds of hyperlactatemia by logistic regression analysis are 4.6 (95% confidence interval 1.4-15; p < 0.05) times higher for a patient with abnormal peripheral perfusion. Conclusions. Subjective assessment of peripheral perfusion with physical examination following initial hemodynamic resuscitation in the first 24 hours of admission could identify hemodynamically stable patients with a more severe organ dysfunction and higher lactate levels. Patients with abnormal peripheral perfusion had significantly higher odds of worsening organ failure than did patients with normal peripheral perfusion following initial resuscitation. (Crit Care Med 2009; 37:934-938)

Objectives: Extracorporeal membrane oxygenation (ECMO) is known to improve cardiorespiratory function and outcome in neonates with severe respiratory failure. In this study, we tested two hypotheses: 1) neonates with severe respiratory failure exhibit alterations of the microcirculation and 2) after ECMO therapy these microcirculatory alterations are improved. Design: Single-center prospective observational study. Setting: Intensive care unit of a level III university children's hospital. Patients: Term neonates receiving venoarterial ECMO. Control patients with and without respiratory failure. Measurements and Main Results: The microcirculation was assessed in the buccal mucosa, using orthogonal polarization spectral imaging, before and after ECMO. Functional capillary density was lower in patients with severe respiratory failure before ECMO (n = 14) compared with control patients (n = 10; p < 0.01). Functional capillary density had increased significantly after ECMO (p < 0.01). Conclusion: Microcirculatory parameters are depressed in neonates with severe respiratory failure and improve significantly following ECMO treatment. (Crit Care Med 2009; 37:1121-1124)

OBJECTIVE: To test the hypothesis that persistent villi hypoperfusion explains intramucosal acidosis after endotoxemic shock resuscitation. DESIGN: Controlled experimental study. SETTING: University-based research laboratory. SUBJECTS: A total of 14 anesthetized, mechanically ventilated sheep. INTERVENTIONS: Sheep were randomly assigned to endotoxin (n = 7) or control groups (n = 7). The endotoxin group received 5 microg/kg endotoxin, followed by 4 microg x kg(-1) x hr(-1) for 150 mins. After 60 mins of shock, hydroxyethylstarch resuscitation was given to normalize oxygen transport for an additional 90 mins. MEASUREMENTS AND MAIN RESULTS: Endotoxin infusion decreased mean arterial blood pressure, cardiac output, and superior mesenteric artery blood flow (96 +/- 10 vs. 51 +/- 20 mm Hg, 145 +/- 30 vs. 90 +/- 30 mL x min(-1) x kg(-1), and 643 +/- 203 vs. 317 +/- 93 mL x min(-1) x kg(-1), respectively; p < .05 vs. basal), whereas it increased intramucosal-arterial PCO2 (deltaPCO2) and arterial lactate (3 +/- 3 vs. 14 +/- 8 mm Hg, and 1.5 +/- 0.5 vs. 3.7 +/- 1.3 mmol/L; p < .05). Sublingual, and serosal and mucosal intestinal microvascular flow indexes, and the percentage of perfused ileal villi were reduced (3.0 +/- 0.1 vs. 2.3 +/- 0.4, 3.2 +/- 0.2 vs. 2.4 +/- 0.6, 3.0 +/- 0.0 vs. 2.0 +/- 0.2, and 98% +/- 3% vs. 76% +/- 10%; p < .05). Resuscitation normalized mean arterial blood pressure (92 +/- 13 mm Hg), cardiac output (165 +/- 32 mL x min(-1) x kg(-1)), superior mesenteric artery blood flow (683 +/- 192 mL x min(-1) x kg(-1)), and sublingual and serosal intestinal microvascular flow indexes (2.8 +/- 0.5 and 3.5 +/- 0.7). Nevertheless, deltaPCO2, lactate, mucosal intestinal microvascular flow indexes, and percentage of perfused ileal villi remained altered (10 +/- 6 mm Hg, 3.7 +/- 0.9 mmol/L, 2.3 +/- 0.4, and 78% +/- 11%; p < .05). CONCLUSIONS: In this model of endotoxemia, fluid resuscitation corrected both serosal intestinal and sublingual microcirculation but was unable to restore intestinal mucosal perfusion. Intramucosal acidosis might be due to persistent villi hypoperfusion

OBJECTIVE: To determine the effects of norepinephrine and levosimendan on microvascular perfusion and oxygenation in a rat model of septic shock. DESIGN: Controlled laboratory animal study. SETTING: Research laboratory in a university hospital. SUBJECTS: Forty Sprague-Dawley rats. INTERVENTIONS: Sepsis was induced in 32 animals by cecal ligation and puncture. Eight animals served as sham controls. Animals were randomly assigned to five groups: 1) fluid resuscitation (25 ml x kg(-1) x h(-1)), 2) fluid resuscitation plus norepinephrine (0.5 microg x kg(-1) x min(-1)), 3) fluid resuscitation plus levosimendan (0.3 microg x kg(-1) x min(-1)), 4) no treatment and 5) sham control. MEASUREMENTS AND MAIN RESULTS: Microvascular perfusion was quantitated using sidestream darkfield imaging and microvascular oxygenation (microPO2) was assessed by oxygen-dependent quenching of phosphorescence. Measurements were obtained on the buccal mucosa at baseline and at hourly intervals thereafter. In parallel, cardiac output (CO) was recorded. After induction of sepsis microvascular perfusion and microPO2 were impaired early followed by significant decreases in CO. Although levosimendan and norepinephrine were equally effective in restoring CO, only treatment with levosimendan significantly improved microPO2 after 1 and 2 hours of treatment (9.7 +/- 2.0 vs. 15.1 +/- 2.6 and 16.0 +/- 3.7 mmHg; p < 0.05). Microvascular perfusion was not significantly influenced by any of the treatment strategies. CONCLUSIONS: In this model, treatment with levosimendan and norepinephrine showed comparable effects in restoring CO and had no significant influence on microvascular perfusion. However, only levosimendan significantly improved microPO2, suggesting that a mechanism relatively independent of macrocirculatory hemodynamics and overall microvascular perfusion might account for these observations

To investigate whether the response to sustained inflation and postinflation positive end-expiratory pressure varies between acute respiratory distress syndrome with pulmonary (ARDS(exp)) and extrapulmonary origin (ARDS(exp)).Prospective clinical study.Multidisciplinary intensive care unit in a university hospital.A total of 11 patients with ARDS and 13 patients with ARDS.A 7 ml/kg tidal volume, 12-15 breaths/min respiratory rate, and an inspiratory/expiratory ratio of 1:2 was used during baseline ventilation. Positive end-expiratory pressure levels were set according to the decision of the primary physician. Sustained inflation was performed by 45 cm H2O continuous positive airway pressure for 30 secs. Postinflation positive end-expiratory pressure was titrated decrementally, starting from a level of 20 cm H2O to keep the peripheral oxygen saturation between 92% and 95%. Fio2 was decreased, and baseline tidal volume, respiratory rate, inspiratory/expiratory ratio were maintained unchanged throughout the study period.Blood gas, airway pressure, and hemodynamic measurements were performed at the following time points: at baseline and at 15 mins, 1 hr, 4 hrs, and 6 hrs after sustained inflation. After sustained inflation, the Pao2/Fio2 ratio improved in all of the patients both in ARDS(p) and ARDS(exp). However, the Pao2/Fio2 ratio increased to200 in four ARDS(p) patients (36%) and in seven ARDS(p) patients (54%). In two of those ARDS patients, the Pao2/Fio2 ratio was found to be200, whereas none of the ARDS(p) patients revealed Pao2/Fio2 ratios of200 at the 6-hr measurement. Postinflation positive end-expiratory pressure levels were set at 16.7 +/- 2.3 cm H O in ARDS(p) and 15.6 +/- 2.5 cm H2O in ARDS. The change in Pao /Fio ratios was found statistically significant in patients with ARDS(p) (p =.0001) and with ARDS(p) (p =.008). Respiratory system compliance increased in ARDS patients (p =.02), whereas the change in ARDS was not statistically significant.Sustained inflation followed by high levels of postinflation positive end-expiratory pressure provided an increase in respiratory system compliance in ARDS; however, arterial oxygenation improved in both ARDS forms.

Objective: To investigate the time course and predictive value of microvascular alterations in children with severe sepsis. Design: Single-center, prospective observational study. Setting: Intensive care unit of a level III university children's hospital. Patients: Patients with septic shock, requiring the administration of fluid and vasopressor agents and/or inotropes after the correction of hypovolemia, who were intubated and ventilated, were included. Interventions: None. Measurements and Main Results: The microcirculation was assessed in the buccal mucosa, using orthogonal polarization spectral imaging, within 24 hrs after admission. Subsequent measurements were performed every 24 hrs for 3 days. The measurements were discontinued when the patient was extubated. There were no significant differences in the functional capillary density or microvascular flow index for all vessel types between survivors and nonsurvivors on day 1. In the survival group, the functional capillary density increased significantly between day 1 and day 2 from 1.7 cm/cm(2) (0.8-3.4) to 4.3 cm/cm(2) (2.1-6.9) (p = .001). Functional capillary density values in nonsurvivors did not change (day 1: 3.2 cm/cm(2) [0.8-3.8]; day 2: 1.9 cm/cm(2) [1.0-2.1]). The median functional capillary density on days 2 and 3 were significantly lower in nonsurvivors (day 2: 1.9 cm/cm(2) [1.0-2.1] vs. 4.3 cm/cm(2) [2.1-6.9], p = .009; day 3: 1.8 cm/cm(2) [1.0-2.0] vs. 4.7 cm/cm(2) [2.1-8.6], p = .01). The microvascular flow index for all vessel types improved in survivors and did not change in nonsurvivors. Differences in microvascular flow index values between survivors and nonsurvivors were not significant. Conclusion: Persistent microcirculatory alterations can be prognostic for survival in children with septic shock. (Crit Care Med 2011; 39:8-13)

OBJECTIVE To determine whether the storage time of human leukodepleted red blood cell concentrates compromises intestinal microvascular oxygen concentration oxygen (muPo(2)) during isovolemic exchange transfusion at low hematocrit. DESIGN Prospective, randomized, controlled study. SETTING University research institute laboratory. SUBJECTS Male Wistar rats. INTERVENTIONS Intestinal muPo(2) was determined by Pd-porphyrin phosphorescence life-time measurements. MEASUREMENTS AND MAIN RESULTS Rats were brought near to a state of oxygen supply dependency by hemodilution with a pasteurized plasma protein solution to a hematocrit of 14.3 +/- 1.1% (n = 24). Subsequently, an isovolemic exchange transfusion with human leukodepleted red blood cells, stored for 2-6 days (fresh, n = 8), 2-3 wks (intermediate, n = 8), or 5-6 wks (old, n = 8), was performed to determine whether intestinal muPo(2) would be preserved. Immunologic reactions were avoided by washing the red blood cell concentrates three times before use. Isovolemic exchange with fresh and intermediate red blood cells maintained muPo(2) whereas old cells decreased muPo(2) with 26%. Subsequent transfusion with red blood cells (hematocrit approximately 60%) until reaching a hematocrit of 32.4 +/- 2.1 % (n = 24) increased intestinal muPo(2) in all three groups to the same extent between 28% and 32%. No changes in red blood cell deformability, as determined by a Laser-assisted Optical Rotational Cell Analyzer, could be demonstrated during 5 wks of storage. CONCLUSION This study shows that at low hematocrit, the oxygen-delivering capacity of human red blood cells stored 5-6 wks is reduced compared with fresh cells and red blood cells stored for an intermediate period. Although red blood cells stored for 2-3 wks are completely devoid of 2,3-diphosphoglycerate, their oxygen-delivering capacity to the intestines was the same as fresh red blood cells. Our study showed that red blood cell deformability was preserved during storage, suggesting that other mechanisms may account for the observed decrease in oxygen delivery by red blood cells stored 2-3 wks.

OBJECTIVE: To review optical spectroscopic techniques for assessment of the determinants of tissue oxygenation and to evaluate the notion that the disturbances in oxygen pathways in sepsis can be accounted for by enhanced functional shunting of parts of the microcirculation. DATA RESOURCES: Experimental data from previous research and the literature were analyzed. STUDY SELECTION: The data selected pertained to a) whether cellular distress in sepsis is caused by tissue hypoxia or disturbed metabolic pathways, b) optical spectroscopic techniques used to study microcirculatory oxygenation, and c) possible mechanisms underlying shunting of the microcirculation in hypoxemia and sepsis. STUDY SYNTHESIS: Despite resuscitation of oxygen-derived variables, signs of regional tissue hypoxia persist in sepsis. The mechanisms underlying this condition are expected to be associated with oxygen pathways in the microcirculation. Optical spectroscopic techniques are providing new insights into these mechanisms. These include absorption spectroscopy for hemoglobin saturation of erythrocytes, reduced nicotinamide adenine dinucleotide fluorescence for tissue mitochondrial bioenergetics, and palladium-porphyrin phosphorescence for microvascular PO2. Reduced nicotinamide adenine dinucleotide videofluorescence studies have shown the heterogeneous nature of hypoxia. Measurement of gut microvascular PO2 in pigs has shown the development of a PO2 gap between microvascular PO2 and venous PO2 during hemorrhage and endotoxemia, with a larger gap occurring in sepsis than in hemorrhage. It is hypothesized that this difference is caused by the enhanced shunting of the microcirculation present in sepsis. CONCLUSIONS: Microcirculatory distress may form one of the earliest stages in the progress of sepsis to multiple organ failure, and shunting of the microcirculation may be an important contributing factor to this development. To evaluate the severity of microcirculatory distress and the effectiveness of resuscitation strategies, new clinical technologies aimed at the microcirculation will need to be developed. It is anticipated that optical spectroscopy will play a major role in the development of such tools

Objective: Current studies concerning selective decontamination of the digestive tract have failed to demonstrate a decrease in the length of hospital stay and mortality rate, despite the finding of a significantly lower number of infections. To evaluate this issue in more detail, the relationship between the mortality rate and length of stay with respect to colonization and infections was studied within a group of patients receiving selective decontamination. Special attention was given to the efficacy of decontamination within each patient. The main question addressed was whether an effect on mortality rate was present, and if so, why this effect was not apparent until now. Design: Prospective observational cohort study. Setting: Surgical intensive care unit (ICU) in a university hospital. Patients: Ninety-seven patients primarily admitted into the surgical ICU who received selective decontamination. Transferred patients were excluded. The majority of the surgeries were elective, and all patients completed the follow-up. Interventions: All patients received polymyxin E, amphotericin B, and norfloxacin four times a day in a 2% solution of Orabaser orally and enterally as suspensions of 200, 500, and 50 mg, respectively. Assessment of the efficacy of selective decontamination was done by identification of Gram-negative microorganisms in surveillance cultures from the oropharynx and rectum. Predicted mortality rates for each patient were calculated with a logistic regression formula. Measurements and Main Results: A possible benefit of selective decontamination of the digestive tract would be expressed by lower actual mortality rates compared to predicted mortality rates. Since we expected the efficacy of decontamination to have an influence on infection and mortality rates, we evaluated these rates in terms of successful or unsuccessful decontamination. Most patients (n = 72) were successfully decontaminated. Actual death rates in these patients were significantly lower than the expected rates (as calculated by the Acute Physiology and Chronic Health Evaluation [APACHE] II scoring system) (18% vs. 40%, p = .006), whereas no difference was found in those patients with failed decontamination (n = 25, death rate 44%). The patients with unsuccessful selective decontamination had significantly longer hospital (52 vs. 34 days) and ICU lengths of stays (23 vs. 9 days; p = .002) and higher mortality rates (44% vs. 18%, p = .020) when compared with those patients who were successfully decontaminated. Conclusions: These results indicate that selective decontamination is beneficial in terms of mortality rate and length of stay in surgical patients only when successful decontamination has been achieved. The subgroup of patients for whom decontamination is not successful might be responsible for the obscurity in mortality effects of selective decontamination in studies until now. It is expected that identification and subsequent elimination of possible risk factors that cause a failure of selective decontamination can result in lower morbidity and mortality rates in critically ill, surgical patients admitted to the ICU. (Crit Care Med 1993; 21:1692–1698)

OBJECTIVES a) To determine the validity of a new method to analyze indicator gas washout tests on mechanically ventilated patients. This method takes into account the difference between the end-expiratory gas fraction and the mean gas fraction in the lung and provides the end-expiratory lung volume and a new index of ventilation inhomogeneity called volumes regression index. b) To determine the validity of this index as a predictor of chronic obstructive pulmonary disease. c) To compare this index with the moment ratio index and Becklake index. DESIGN Prospective study of diagnostic test. Criterium standards: Closed-circuit indicator gas dilution technique and Tiffeneau index. SETTING Surgical intensive care unit of a university hospital. PATIENTS A total of 38 mechanically ventilated postoperative patients, divided into two groups: the obstructive group (n = 21) and the nonobstructive group (n = 17), based on their preoperative lung function. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS a) The mean coefficient of variation of all lung volume measurements in a group of nine healthy volunteers was 5%, and the difference between this technique and the closed-circuit helium dilution measurements was -2 +/- 5%. In patients, the mean coefficient of variation of the lung volume measurements was 3.5%. The volumes regression index was measured as 0.02 +/- 0.04 in a dummy lung, 0.37 +/- 0.08 in the healthy volunteers, 0.64 +/- 0.23 in the nonobstructive patients, and 1.1 +/- 0.3 in the obstructive patients. The volumes regression index provided a better correlation (r2 = .46) with preoperatively determined Tiffeneau index than the Becklake index (r2 = .11) or the moment ratio index (r2 = .18). CONCLUSION The proposed technique provides a means for accurate measurement of the end-expiratory lung volume and the amount of ventilation inhomogeneity in mechanically ventilated intensive care unit patients.

A device to produce a stepwise indicator gas fraction variation to initiate a washout test in mechanically ventilated patients is described. The device, which can be used in conjunction with the commonly used Siemens-Elema series 900 ventilators, is based on simple, off-the-shelf technology. It features the simultaneous use of two indicator gases (so that the influence of diffusion processes in the gas exchange to the patient can be measured) and maintains a nearly constant FIO2 during a washout procedure. With this indicator gas injector, the transition time of the indicator gas fraction at the beginning of a washout proved to be short enough to detect ventilation inhomogeneity by visual inspection of the washout curves. Functional residual capacity measurements using this device are presented on a test lung with known volume, on healthy volunteers, and on critically ill patients.