Presence of Genetic Variants Among Young Men With Severe COVID-19.

Importance: Severe coronavirus disease 2019 (COVID-19) can occur in younger, predominantly male, patients without preexisting medical conditions. Some individuals may have primary immunodeficiencies that predispose to severe infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objective: To explore the presence of genetic variants associated with primary immunodeficiencies among young patients with COVID-19. Design, Setting, and Participants: Case series of pairs of brothers without medical history meeting the selection criteria of young (age <35 years) brother pairs admitted to the intensive care unit (ICU) due to severe COVID-19. Four men from 2 unrelated families were admitted to the ICUs of 4 hospitals in the Netherlands between March 23 and April 12, 2020. The final date of follow-up was May 16, 2020. Available family members were included for genetic variant segregation analysis and as controls for functional experiments. Exposure: Severe COVID-19. Main Outcome and Measures: Results of rapid clinical whole-exome sequencing, performed to identify a potential monogenic cause. Subsequently, basic genetic and immunological tests were performed in primary immune cells isolated from the patients and family members to characterize any immune defects. Results: The 4 male patients had a mean age of 26 years (range, 21-32), with no history of major chronic disease. They were previously well before developing respiratory insufficiency due to severe COVID-19, requiring mechanical ventilation in the ICU. The mean duration of ventilatory support was 10 days (range, 9-11); the mean duration of ICU stay was 13 days (range, 10-16). One patient died. Rapid clinical whole-exome sequencing of the patients and segregation in available family members identified loss-of-function variants of the X-chromosomal TLR7. In members of family 1, a maternally inherited 4-nucleotide deletion was identified (c.2129_2132del; p.[Gln710Argfs*18]); the affected members of family 2 carried a missense variant (c.2383G>T; p.[Val795Phe]). In primary peripheral blood mononuclear cells from the patients, downstream type I interferon (IFN) signaling was transcriptionally downregulated, as measured by significantly decreased mRNA expression of IRF7, IFNB1, and ISG15 on stimulation with the TLR7 agonist imiquimod as compared with family members and controls. The production of IFN-γ, a type II IFN, was decreased in patients in response to stimulation with imiquimod. Conclusions and Relevance: In this case series of 4 young male patients with severe COVID-19, rare putative loss-of-function variants of X-chromosomal TLR7 were identified that were associated with impaired type I and II IFN responses. These preliminary findings provide insights into the pathogenesis of COVID-19.

Postural change in volunteers: sympathetic tone determines microvascular response to cardiac preload and output increases.

PURPOSE: Microvascular perfusion may be a non-invasive indicator of fluid responsiveness. We aimed to investigate which of the microvascular perfusion parameters truly reflects fluid responsiveness independent of sympathetic reflexes. METHODS: Fifteen healthy volunteers underwent a postural change from head up tilt (HUT) to the supine position, diminishing sympathetic tone, followed by a 30° passive leg raising (PLR) with unaltered tone. Prior to and after the postural changes, stroke volume (SV) and cardiac output (CO) were measured, as well as sublingual microcirculatory perfusion (sidestream dark field imaging), skin perfusion, and oxygenation (laser Doppler flowmetry and reflectance spectroscopy). RESULTS: In responders (subjects with >10 % increase in CO), the HUT to supine change increased CO, SV, and pulse pressure, while heart rate, systemic vascular resistance, and mean arterial pressure decreased. Additionally, microvascular flow index, laser Doppler flow, and microvascular hemoglobin oxygen saturation and concentration also increased. CONCLUSION: When preload and forward flow increase in association with a decrease in sympathetic activity, microvascular blood flow increases in the skin and in the sublingual area. When preload and forward flow increase with little to no change in sympathetic activity, only sublingual functional capillary density increases. Therefore, our results indicate that sublingual functional capillary density is the best parameter to use when evaluating fluid responsiveness independent of changes in sympathetic tone.

Peripheral Perfusion Index Predicts Hypotension during Fluid Withdrawal by Continuous Veno-Venous Hemofiltration in Critically Ill Patients.

AIM: Peripheral perfusion may predict harmful hypovolemic hypotension during fluid withdrawal by continuous veno-venous hemofiltration (CVVH) in critically ill patients with acute kidney injury. METHODS: Twenty-three critically ill AKI patients were subjected to progressive fluid withdrawal. Systemic hemodynamics and peripheral perfusion index (PPI) by pulse oximetry, forearm-to-fingertip skin temperature gradient (Tskin-diff) and tissue oxygen saturation (StO2, near infra-red spectroscopy) were measured. RESULTS: Most hemodynamic values decreased with fluid withdrawal, particularly in the hypotensive group, except for stroke volume (SV) and cardiac output, which decreased to a great extent in the non-hypotensive patients. Increases in systemic vascular resistance (SVR) were less in hypotension. Baseline pulse pressure and PPI were lower in hypotensive (n = 10) than non-hypotensive patients and subsequent PPI values paralleled SV decreases. A baseline PPI ≤0.82 AU predicted hypotension with a sensitivity of 70%, and a specificity of 92% (AUC 0.80 ± 0.11, p = 0.004). CONCLUSION: Progressive fluid withdrawal during CVVH is poorly tolerated in patients with less increases in SVR. The occurrence of hypotension can be predicted by low baseline PPI.

Tissue perfusion and oxygenation to monitor fluid responsiveness in critically ill, septic patients after initial resuscitation: a prospective observational study.

Fluid therapy after initial resuscitation in critically ill, septic patients may lead to harmful overloading and should therefore be guided by indicators of an increase in stroke volume (SV), i.e. fluid responsiveness. Our objective was to investigate whether tissue perfusion and oxygenation are able to monitor fluid responsiveness, even after initial resuscitation. Thirty-five critically ill, septic patients underwent infusion of 250 mL of colloids, after initial fluid resuscitation. Prior to and after fluid infusion, SV, cardiac output sublingual microcirculatory perfusion (SDF: sidestream dark field imaging) and skin perfusion and oxygenation (laser Doppler flowmetry and reflectance spectroscopy) were measured. Fluid responsiveness was defined by a ≥5 or 10% increase in SV upon fluids. In responders to fluids, SDF-derived microcirculatory and skin perfusion and oxygenation increased, but only the increase in cardiac output, mean arterial and pulse pressure, microvascular flow index and relative Hb concentration and oxygen saturation were able to monitor a SV increase. Our proof of principle study demonstrates that non-invasively assessed tissue perfusion and oxygenation is not inferior to invasive hemodynamic measurements in monitoring fluid responsiveness. However skin reflectance spectroscopy may be more helpful than sublingual SDF.

Microvascular perfusion as a target for fluid resuscitation in experimental circulatory shock.

OBJECTIVES: To study regional perfusion during experimental endotoxemic and obstructive shock and compare the effect of initial cardiac output-targeted fluid resuscitation with optimal cardiac output-targeted resuscitation on different peripheral tissues. DESIGN: Controlled experimental study. SETTING: University-affiliated research laboratory. SUBJECTS: Fourteen fasted anesthetized mechanically ventilated domestic pigs. INTERVENTIONS: Domestic pigs were randomly assigned to the endotoxemic (n = 7) or obstructive shock (n = 7) model. Central and regional perfusion parameters were obtained at baseline, during greater than or equal to 50% reduction of cardiac output (T1), after initial resuscitation to baseline (T2), and after optimization of cardiac output (T3). MEASUREMENTS AND MAIN RESULTS: Regional perfusion was assessed in the sublingual, intestinal, and muscle vascular beds at the different time points and included visualization of the microcirculation, measurement of tissue oxygenation, and indirect assessments of peripheral skin perfusion. Hypodynamic shock (T1) simultaneously decreased all regional perfusion variables in both models. In the obstructive model, these variables returned to baseline levels at T2 and remained in this range after T3, similar to cardiac output. In the endotoxemic model, however, the different regional perfusion variables were only normalized at T3 associated with the hyperdynamic state at this point. The magnitude of changes over time between the different vascular beds was similar in both models, but the endotoxemic model displayed greater heterogeneity between tissues. CONCLUSIONS: This study demonstrates that the relationship between the systemic and regional perfusion is dependent on the underlying cause of circulatory shock. Further research will have to demonstrate whether different microvascular perfusion variables can be used as additional resuscitation endpoints.

Nitroglycerin reverts clinical manifestations of poor peripheral perfusion in patients with circulatory shock.

INTRODUCTION: Recent clinical studies have shown a relationship between abnormalities in peripheral perfusion and unfavorable outcome in patients with circulatory shock. Nitroglycerin is effective in restoring alterations in microcirculatory blood flow. The aim of this study was to investigate whether nitroglycerin could correct the parameters of abnormal peripheral circulation in resuscitated circulatory shock patients. METHODS: This interventional study recruited patients who had circulatory shock and who persisted with abnormal peripheral perfusion despite normalization of global hemodynamic parameters. Nitroglycerin started at 2 mg/hour and doubled stepwise (4, 8, and 16 mg/hour) each 15 minutes until an improvement in peripheral perfusion was observed. Peripheral circulation parameters included capillary refill time (CRT), skin-temperature gradient (Tskin-diff), perfusion index (PI), and tissue oxygen saturation (StO2) during a reactive hyperemia test (RincStO2). Measurements were performed before, at the maximum dose, and after cessation of nitroglycerin infusion. Data were analyzed by using linear model for repeated measurements and are presented as mean (standard error). RESULTS: Of the 15 patients included, four patients (27%) responded with an initial nitroglycerin dose of 2 mg/hour. In all patients, nitroglycerin infusion resulted in significant changes in CRT, Tskin-diff, and PI toward normal at the maximum dose of nitroglycerin: from 9.4 (0.6) seconds to 4.8 (0.3) seconds (P < 0.05), from 3.3 °C (0.7 °C) to 0.7 °C (0.6 °C) (P < 0.05), and from [log] -0.5% (0.2%) to 0.7% (0.1%) (P < 0.05), respectively. Similar changes in StO2 and RincStO2 were observed: from 75% (3.4%) to 84% (2.7%) (P < 0.05) and 1.9%/second (0.08%/second) to 2.8%/second (0.05%/second) (P < 0.05), respectively. The magnitude of changes in StO2 was more pronounced for StO2 of less than 75%: 11% versus 4%, respectively (P < 0.05). CONCLUSIONS: Dose-dependent infusion of nitroglycerin reverted abnormal peripheral perfusion and poor tissue oxygenation in patients following circulatory shock resuscitation. Individual requirements of nitroglycerin dose to improve peripheral circulation vary between patients. A simple and fast physical examination of peripheral circulation at the bedside can be used to titrate nitroglycerin infusion.

Fluid therapy in the acute brain injured patient.

Adequate fluid therapy in the acute brain injured (ABI) patient is essential for maintaining an adequate brain and systemic physiology and preventing intra- and extracranial complications. The target of euvolemia, implying avoidance of both hypovolemia and fluid overloading (or "hypervolemia," by definition associated with fluid extravasation leading to tissue edema) is of key importance. Primary brain injury can be aggravated by secondary brain injury and systemic deterioration through diverse pathways which can challenge appropriate fluid management, e.g. neuroendocrine and electrolyte disorders, stress cardiomyopathy (also known as cardiac stunning) and neurogenic pulmonary edema. This is an updated expert opinion aiming to provide a practical overview on fluid therapy in the ABI patient, partly based on more recent work and stressing the fact that intravenous fluids should be regarded as drugs, with their inherent potential for both benefit and (unintended) harm.

The relation of near-infrared spectroscopy with changes in peripheral circulation in critically ill patients.

OBJECTIVE: We conducted this observational study to investigate tissue oxygen saturation during a vascular occlusion test in relationship with the condition of peripheral circulation and outcome in critically ill patients. DESIGN: Prospective observational study. SETTING: Multidisciplinary intensive care unit in a university hospital. PATIENTS: Seventy-three critically ill adult patients admitted to the intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were followed every 24 hrs until day 3 after intensive care admission. Near-infrared spectroscopy was used to measure thenar tissue oxygen saturation, tissue oxygen saturation deoxygenation rate, and tissue oxygen saturation recovery rate after the vascular occlusion test. Measurements included heart rate, mean arterial pressure, forearm-to-fingertip skin-temperature gradient, and physical examination of peripheral perfusion with capillary refill time. Patients were stratified according to the condition of peripheral circulation (abnormal: forearm-to-fingertip skin-temperature gradient ≥4 and capillary refill time >4.5 secs). The outcome was defined based on the daily Sequential Organ Failure Assessment score and blood lactate levels. Upon intensive care unit admission, 35 (47.9%) patients had abnormal peripheral perfusion (forearm-to-fingertip skin-temperature gradient >4 or capillary refill time >4.5 secs). With the exception of the tissue oxygen saturation deoxygenation rate, tissue oxygen saturation baseline and tissue oxygen saturation recovery rate were statistically lower in patients who exhibited abnormal peripheral perfusion than in those with normal peripheral perfusion: 72 ± 9 vs. 81 ± 9; p = .001 and 1.9 ± 0.7 vs. 3.2 ± 0.9; p = .001, respectively. When a mixed-model analysis was performed over time for estimate (s) calculation, adjusted to the condition of disease, we did not find a significant clinical effect between vascular occlusion test-derived tissue oxygen saturation measurements (as response variables) and mean systemic hemodynamic variables (as independent variables): tissue oxygen saturation vs. heart rate: s (95% confidence interval) = 0.007 (-0.08; 0.09); tissue oxygen saturation vs. mean arterial pressure: s (95% confidence interval) = -0.02 (-0.12; 0.08); tissue oxygen saturation deoxygenation rate vs. heart rate: s (95% confidence interval) = 0.002 (-0.0004; 0.006); tissue oxygen saturation deoxygenation rate vs. mean arterial pressure: s (95% confidence interval) - 0.0007 (-0.003; 0.004); tissue oxygen saturation recovery rate vs. heart rate: s (95% confidence interval) = -0.009 (-0.02; -0.0015); tissue oxygen saturation recovery rate vs. mean arterial pressure: s (95% confidence interval) = 0.01 (0.002; 0.018). However, there was a strong association between tissue oxygen saturation baseline and tissue oxygen saturation recovery rate with abnormal peripheral perfusion: tissue oxygen saturation vs. abnormal peripheral perfusion: s (95% confidence interval) = -10.1 (-13.9; -6.2); tissue oxygen saturation recovery rate vs. abnormal peripheral perfusion: s (95% confidence interval) =-10.1 (-13.9; -6.2); tissue oxygen saturation recovery rate vs. abnormal peripheral perfusion: s (95% confidence interval) = -1.1 (-1.4; -0.81). Poor outcome was more closely related to abnormalities in peripheral perfusion than to tissue oxygen saturation-derived parameters. CONCLUSIONS: We found that the condition of peripheral circulation in critically ill patients strongly influences tissue oxygen saturation resting values and the tissue oxygen saturation reoxygenation rate but not the tissue oxygen saturation deoxygenation rate. In addition, changes in near-infrared spectroscopy-derived variables were independent of condition of disease and were not accompanied by any major differences in systemic hemodynamic variables.

Virtual Reality to Improve Sequelae of the Postintensive Care Syndrome: A Multicenter, Randomized Controlled Feasibility Study.

Psychologic sequelae after critical illness, part of the postintensive care syndrome, significantly decrease quality of life. A robustly effective treatment intervention is currently lacking. Virtual reality has beneficial effects on several non-ICU-related psychologic disorders. The aim of this study was to explore patient-related determinants of ICU-specific virtual reality, such as the timing of patients' self-reported readiness to initiate virtual reality and the number of desired sessions and safety, and to explore the effects of ICU-specific virtual reality on mental health. DESIGN: A multicenter, randomized controlled feasibility study. SETTING: ICU at a university teaching hospital and a secondary care hospital in Rotterdam, The Netherlands. PATIENTS: Consecutive mechanically ventilated patients with sepsis or septic shock. INTERVENTIONS: Patients were randomly assigned (1:1) to receive ICU-specific virtual reality (ICU-specific virtual reality group) or exposure to a nature virtual reality environment (control virtual reality group). MEASUREMENT AND MAIN RESULTS: Explorative outcomes were feasibility, in terms of patient-related determinants, and safety. The effects of ICU-specific virtual reality on the psychologic components of postintensive care syndrome and quality of life were additionally studied. Fifty patients (median age: 61 yr; 21 [42%] female) were included. Patients in the ICU-specific virtual reality group felt ready to initiate the virtual reality intervention 10 days (median, 95% range, 5-21 d) after ICU discharge, and one session (median, 95% range, 1-6) was desired. ICU-specific virtual reality patients experienced higher immersion, cybersickness scores were low, and no changes in vital signs were observed. They also reported reduced posttraumatic stress disorder and depression scores and better mental health from 2 days until 1 month after initial exposure (Short Form-12 Mental Component Scale: ICU-specific virtual reality, 57 [36-67] vs control virtual reality, 47 [26-63]; p < 0.01). Six months after exposure, this effect was still present for posttraumatic stress disorder and depression, but not for mental quality of life. CONCLUSIONS: ICU-specific virtual reality is a feasible and acceptable novel intervention that could be used during recovery from an episode of critical illness in the ICU. A future, adequately powered study should confirm whether virtual reality is able to improve mental health and quality of life.

Psychologic Distress and Quality of Life After ICU Treatment for Coronavirus Disease 2019: A Multicenter, Observational Cohort Study.

To quantify short- and long-term psychologic distress, that is, symptoms of posttraumatic stress disorder, anxiety, and depression, and the health-related quality of life in coronavirus disease 2019 ICU survivors. DESIGN: A prospective, observational cohort study. SETTING: Postcoronavirus disease 2019 clinics of three hospitals in Rotterdam, the Netherlands. PATIENTS: Adult patients admitted for coronavirus disease 2019 to the ICU, who visited the postcoronavirus disease 2019 follow-up clinic. MEASURES AND MAIN RESULTS: The primary outcomes were psychologic distress and overall and mental health-related quality of life, assessed using the Impact of Event Scale-Revised, Hospital Anxiety and Depression Scale, Short-Form 36, and European Quality of Life 5D, 6 weeks, 3 months, and 6 months post hospital discharge. Second, we compared 3-month psychologic and mental health-related quality of life outcomes with a historical critical illness survivor cohort and overall and mental health-related quality of life with the Dutch population. We included 118 patients with a median age of 61 years (95% range, 36-77 yr) of whom 79 (68%) were male. At 6 weeks, 13 patients (23%) reported psychologic distress, copresence of probable psychiatric disorders was common, and no decline in psychologic distress was observed throughout follow-up. Coronavirus disease 2019 patients tend to suffer less from posttraumatic stress disorder and reported less severe symptoms of anxiety (Hospital Anxiety and Depression Scale Anxiety Score: 3 [0-17] vs 5 [0-16]; estimated mean difference 2.3 [95% CI, 0.0-4.7]; p = 0.05) and depression (Hospital Anxiety and Depression Scale Depression Score: 3 [0-15] vs 5 [0-16]; estimated mean difference 2.4 [95% CI, 0.1-2.4]; p = 0.04) than the historical critical illness cohort. Overall and mental health-related quality of life increased over time. Coronavirus disease 2019 ICU survivors reported better mental health-related quality of life than our historical cohort, but overall and mental health-related quality of life was still poorer than the Dutch population. CONCLUSIONS: Psychologic distress was common in coronavirus disease 2019 ICU survivors and remained similar until 6 months after hospital discharge. Health-related quality of life increased over time and was higher than in a historical cohort, but was lower than in the Dutch population. Our findings highlight that coronavirus disease 2019 ICU survivors should be monitored after ICU treatment to detect possible psychologic distress.

Virtual reality for relatives of ICU patients to improve psychological sequelae: study protocol for a multicentre, randomised controlled trial.

INTRODUCTION: Intensive care unit (ICU) admission of a relative might lead to psychological distress and complicated grief (post-intensive care syndrome-family; PICS-F). Evidence suggests that increased distress during ICU stay increases risk of PICS-F, resulting in difficulty returning to their normal lives after the ICU experience. Effective interventions to improve PICS-F are currently lacking. In the present trial, we hypothesised that information provision using ICU-specific Virtual Reality for Family members/relatives (ICU-VR-F) may improve understanding of the ICU and subsequently improve psychological well-being and quality of life in relatives of patients admitted to the ICU. METHODS AND ANALYSIS: This multicentre, clustered randomised controlled trial will be conducted from January to December 2021 in the mixed medical-surgical ICUs of four hospitals in Rotterdam, the Netherlands. We aim to include adult relatives of 160 ICU patients with an expected ICU length of stay over 72 hours. Participants will be randomised clustered per patient in a 1:1 ratio to either the intervention or control group. Participants allocated to the intervention group will receive ICU-VR-F, an information video that can be watched in VR, while the control group will receive usual care. Initiation of ICU-VR-F will be during their hospital visit unless participants cannot visit the hospital due to COVID-19 regulations, then VR can be watched digitally at home. The primary objective is to study the effect of ICU-VR-F on psychological well-being and quality of life up to 6 months after the patients' ICU discharge. The secondary outcome is the degree of understanding of ICU treatment and ICU modalities. ETHICS AND DISSEMINATION: The Medical Ethics Committee of the Erasmus Medical Centre, Rotterdam, the Netherlands, approved the study and local approval was obtained from each participating centre (NL73670.078.20). Our findings will be disseminated by presentation of the results at (inter)national conferences and publication in scientific, peer-reviewed journals. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (TrialRegister.nl, NL9220).

Real-time assessment of renal cortical microvascular perfusion heterogeneities using near-infrared laser speckle imaging.

Laser speckle imaging (LSI) is able to provide full-field perfusion maps of the renal cortex and allows quantification of the average LSI perfusion within an arbitrarily set region of interest and the recovery of LSI perfusion histograms within this region. The aim of the present study was to evaluate the use of LSI for mapping renal cortical microvascular perfusion and to demonstrate the capability of LSI to assess renal perfusion heterogeneities. The main findings were that: 1) full-field LSI measurements of renal microvascular perfusion were highly correlated to single-point LDV measurements; 2) LSI is able to detect differences in reperfusion dynamics following different durations of ischemia; and 3) renal microvascular perfusion heterogeneities can be quantitatively assessed by recovering LSI perfusion histograms.

Validation of near-infrared laser speckle imaging for assessing microvascular (re)perfusion.

The present study was conducted to compare laser speckle imaging (LSI) with sidestream dark field (SDF) imaging (i.e., capillary microscopy) so as to validate the use of LSI for assessing microvascular (re)perfusion. For this purpose, LSI and SDF measurements were performed on the human nail fold during gradual occlusion of the upperarm circulation to modify nail fold perfusion under controlled circumstances. Additionally, a vascular occlusion test was performed to test the ability of LSI to detect rapid changes in tissue perfusion during reactive hyperemia and a hyperthermic challenge was performed to measure LSI perfusion at maximum functional capillary density. Normalized LSI measurements (i.e., normalized to baseline is 100%) were shown to correlate positively with normalized SDF measurements (Pearson's r=0.92). This was supported by linear regression analysis (slope of 1.01, R(2)=0.85, p<0.001). During the vascular occlusion test, LSI perfusion decreased from 307+/-90 AU (baseline) to 42+/-8 AU (ischemia). Peak perfusion during reperfusion was 651+/-93 AU (212% of baseline), which had returned to baseline after 2 min. Hyperthermia increased LSI perfusion from 332+/-90 AU to 1067+/-256 AU (321% of baseline). The main finding was that changes in perfusion as measured by LSI correlated well with changes in capillary red blood cell velocities as measured by SDF imaging during controlled reduction of the (micro)vascular perfusion. It was further shown that LSI is capable of measuring tissue perfusion at high temporal and spatial resolution. In conclusion, LSI can be employed to accurately quantitate microvascular reactivity following ischemic and hyperthermic challenges.

The effect of perfusion pressure on gastric tissue blood flow in an experimental gastric tube model.

BACKGROUND: Anastomotic leakage and stricture formation remain an important surgical challenge after esophagectomy with gastric tube reconstruction for cancer of the esophagus. The perfusion of the anastomotic site at the proximal site of the gastric tube depends exclusively on the microcirculation, making it susceptible to hypoperfusion. We hypothesized that increasing the perfusion pressure would improve blood flow at the anastomotic site of the gastric tube. METHODS: A gastric tube was reconstructed in 9 pigs. Laser speckle imaging and thermographic imaging were used to measure blood flow and temperature, respectively, at the base, medial part, future anastomotic site, and top of the gastric tube. Measurements were repeated at every stepwise increase of mean arterial blood pressure (MAP) from 50 to 110 mm Hg. RESULTS: Besides MAP, global hemodynamics did not change throughout the experiment. The blood flow in the top of the gastric tube was significantly lower than the flow in the base and medial part of the gastric tube at all levels of MAP. Increasing MAP did not have a significant effect on blood flow at any location in the gastric tube. Distribution of temperature was similar to distribution of flow for the different locations. Increases in MAP did not change temperature values at any location of the gastric tube. CONCLUSION: Blood flow in the upper part of the gastric tube is decreased compared with more proximal sites. Gastric tissue blood flow does not increase with increased perfusion pressure. Therefore, it is not recommended to increase MAP to supranormal levels to increase anastomotic tissue blood flow and reduce postoperative complications.

Assessment of tissue oxygen saturation during a vascular occlusion test using near-infrared spectroscopy: the role of probe spacing and measurement site studied in healthy volunteers.

INTRODUCTION: To assess potential metabolic and microcirculatory alterations in critically ill patients, near-infrared spectroscopy (NIRS) has been used, in combination with a vascular occlusion test (VOT), for the non-invasive measurement of tissue oxygen saturation (StO2), oxygen consumption, and microvascular reperfusion and reactivity. The methodologies for assessing StO2 during a VOT, however, are very inconsistent in the literature and, consequently, results vary from study to study, making data comparison difficult and potentially inadequate. Two major aspects concerning the inconsistent methodology are measurement site and probe spacing. To address these issues, we investigated the effects of probe spacing and measurement site using 15 mm and 25 mm probe spacings on the thenar and the forearm in healthy volunteers and quantified baseline, ischemic, reperfusion, and hyperemic VOT-derived StO2 variables. METHODS: StO2 was non-invasively measured in the forearm and thenar in eight healthy volunteers during 3-minute VOTs using two InSpectra tissue spectrometers equipped with a 15 mm probe or a 25 mm probe. VOT-derived StO2 traces were analyzed for base-line, ischemic, reperfusion, and hyperemic parameters. Data were categorized into four groups: 15 mm probe on the forearm (F15 mm), 25 mm probe on the forearm (F25 mm), 15 mm probe on the thenar (T15 mm), and 25 mm probe on the thenar (T25 mm). RESULTS: Although not apparent at baseline, probe spacing and measurement site significantly influenced VOT-derived StO2 variables. For F15 mm, F25 mm, T15 mm, and T25 mm, StO2 ownslope was -6.4 +/- 1.7%/minute, -10.0 +/- 3.2%/minute, -12.5 +/- 3.0%/minute, and -36.7 +/- 4.6%/minute, respectively. StO2 upslope was 105 +/- 34%/minute, 158 +/- 55%/minute, 226 +/- 41%/minute, and 713 +/- 101%/minute, and the area under the hyperemic curve was 7.4 +/- 3.8%.minute, 10.1 +/- 4.9%.minute, 12.6 +/- 4.4%.minute, and 21.2 +/- 2.7%.minute in these groups, respectively. Furthermore, the StO2 parameters of the hyperemic phase of the VOT, such as the area under the curve, significantly correlated to the minimum StO2 during ischemia. CONCLUSIONS: NIRS measurements in combination with a VOT are measurement site-dependent and probe-dependent. Whether this dependence is anatomy-, physiology-, or perhaps technology-related remains to be elucidated. Our study also indicated that reactive hyperemia depends on the extent of ischemic insult.

Simultaneous multi-depth assessment of tissue oxygen saturation in thenar and forearm using near-infrared spectroscopy during a simple cardiovascular challenge.

INTRODUCTION: Hypovolemia and hypovolemic shock are life-threatening conditions that occur in numerous clinical scenarios. Near-infrared spectroscopy (NIRS) has been widely explored, successfully and unsuccessfully, in an attempt to use it as an early detector of hypovolemia by measuring tissue oxygen saturation (StO2). In order to investigate the measurement site dependence and probe dependence of NIRS in response to hemodynamic changes, such as hypovolemia, we applied a simple cardiovascular challenge: a posture change from supine to upright, causing a decrease in stroke volume (as in hypovolemia) and a heart rate increase in combination with peripheral vasoconstriction to maintain adequate blood pressure. METHODS: Multi-depth NIRS was used in nine healthy volunteers to assess changes in StO2 in the thenar and forearm in response to the hemodynamic changes associated with a posture change from supine to upright. RESULTS: A posture change from supine to upright resulted in a significant increase (P < 0.001) in heart rate. Thenar StO2 did not respond to the hemodynamic changes following the posture change, whereas forearm StO2 did. Forearm StO2 was significantly lower (P < 0.001) in the upright position compared to supine for all probing depths. CONCLUSIONS: The primary findings in this study were that forearm StO2 is a more sensitive parameter to hemodynamic changes than thenar StO2 and that the depth at which StO2 is measured is of minor influence. Our data support the use of forearm StO2 as a sensitive parameter for the detection of central hypovolemia and hypovolemic shock in (trauma) patients.