Low Perfusion and Missed Diagnosis of Hypoxemia by Pulse Oximetry in Darkly Pigmented Skin: A Prospective Study.

BACKGROUND: Retrospective clinical trials of pulse oximeter accuracy report more frequent missed diagnoses of hypoxemia in hospitalized Black patients than White patients, differences that may contribute to racial disparities in health and health care. Retrospective studies have limitations including mistiming of blood samples and oximeter readings, inconsistent use of functional versus fractional saturation, and self-reported race used as a surrogate for skin color. Our objective was to prospectively measure the contributions of skin pigmentation, perfusion index (PI), sex, and age on pulse oximeter errors in a laboratory setting. METHODS: We enrolled 146 healthy subjects, including 25 with light skin (Fitzpatrick class I and II), 78 with medium (class III and IV), and 43 with dark (class V and VI) skin. We studied 2 pulse oximeters (Nellcor N-595 and Masimo Radical 7) in prevalent clinical use. We analyzed 9763 matched pulse oximeter readings (pulse oximeter measured functional saturation [Sp o2 ]) and arterial oxygen saturation (hemoximetry arterial functional oxygen saturation [Sa o2 ]) during stable hypoxemia (Sa o2 68%-100%). PI was measured as percent infrared light modulation by the pulse detected by the pulse oximeter probe, with low perfusion categorized as PI < 1%. The primary analysis was to assess the relationship between pulse oximeter bias (difference between Sa o2 and Sp o2 ) by skin pigment category in a multivariable mixed-effects model incorporating repeated-measures and different levels of Sa o2 and perfusion. RESULTS: Skin pigment, PI, and degree of hypoxemia significantly contributed to errors (bias) in both pulse oximeters. For PI values of 1.0% to 1.5%, 0.5% to 1.0%, and <0.5%, the P value of the relationship to mean bias or median absolute bias was <.00001. In lightly pigmented subjects, only PI was associated with positive bias, whereas in medium and dark subjects bias increased with both low perfusion and degree of hypoxemia. Sex and age was not related to pulse oximeter bias. The combined frequency of missed diagnosis of hypoxemia (pulse oximeter readings 92%-96% when arterial oxygen saturation was <88%) in low perfusion conditions was 1.1% for light, 8.2% for medium, and 21.1% for dark skin. CONCLUSIONS: Low peripheral perfusion combined with darker skin pigmentation leads to clinically significant high-reading pulse oximeter errors and missed diagnoses of hypoxemia. Darkly pigmented skin and low perfusion states are likely the cause of racial differences in pulse oximeter performance in retrospective studies.

Reducing Volatile Anesthetic Waste Using a Commercial Electronic Health Record Clinical Decision Support Tool to Lower Fresh Gas Flows.

BACKGROUND: Volatile anesthetic consumption can be reduced by minimizing excessive fresh gas flows (FGFs). Currently, it is unknown whether decision support tools embedded within commercial electronic health record systems can be successfully adopted to achieve long-term reductions in FGF rates. The authors describe the implementation of an electronic health record-based clinical decision support tool aimed at reducing FGF and evaluate the effectiveness of this intervention in achieving sustained reductions in FGF rates and volatile anesthetic consumption. METHODS: On August 29, 2018, we implemented a decision support tool within the Epic Anesthesia Information Management System (AIMS) to alert providers of high FGF (>0.7 L/min for desflurane and >1 L/min for sevoflurane) during maintenance of anesthesia. July 22, 2015, to July 10, 2018, served as our baseline period before the intervention. The intervention period spanned from August 29, 2018, to December 31, 2019. Our primary outcomes were mean FGF (L/min) and volatile agent consumption (mL/MAC-h). Because a simple comparison of 2 time periods may result in false conclusions due to underlying trends independent of the intervention, we performed segmented regression of the interrupted time series to assess the change in level at the start of the intervention and the differences in slopes before and after the intervention. The analysis was also adjusted for potential confounding variables. Data included 44,899 cases using sevoflurane preintervention with 26,911 cases postintervention, and 17,472 cases using desflurane with 1185 cases postintervention. RESULTS: Segmented regression of the interrupted times series demonstrated a decrease in mean FGF by 0.6 L/min (95% CI, 0.6-0.6 L/min; P < .0001) for sevoflurane and 0.2 L/min (95% CI, 0.2-0.3 L/min; P < .0001) for desflurane immediately after implementation of the intervention. For sevoflurane, mL/MAC-h decreased by 3.8 mL/MAC-h (95% CI, 3.6-4.1 mL/MAC-h; P < .0001) after implementation of the intervention and decreased by 4.1 mL/MAC-h (95% CI, 2.6-5.6 mL/MAC-h; P < .0001) for desflurane. Slopes for both FGF and mL/MAC-h in the postintervention period were statistically less negative than the preintervention slopes (P < .0001 for sevoflurane and P < .01 for desflurane). CONCLUSIONS: A commercial AIMS-based decision support tool can be adopted to change provider FGF management patterns and reduce volatile anesthetic consumption in a sustainable fashion.

Quantifying pulse oximeter accuracy during hypoxemia and severe anemia using an in vitro circulation system.

Anemia and hypoxemia are common clinical conditions that are difficult to study and may impact pulse oximeter performance. Utilizing an in vitro circulation system, we studied performance of three pulse oximeters during hypoxemia and severe anemia. Three oximeters including one benchtop, one handheld, and one fingertip device were selected to reflect a range of cost and device types. Human blood was diluted to generate four hematocrit levels (40%, 30%, 20%, and 10%). Oxygen and nitrogen were bubbled through the blood to generate a range of oxygen saturations (O2Hb) and the blood was cycled through the in vitro circulation system. Pulse oximeter saturations (SpO2) were paired with simultaneously-measured O2Hb readings from a reference CO-oximeter. Data for each hematocrit level and each device were least-squares fit to a 2nd-order equation with quality of each curve fit evaluated using standard error of the estimate. Bias and average root mean square error were calculated after correcting for the calibration difference between human and in vitro circulation system calibration. The benchtop oximeter maintained good accuracy at all but the most extreme level of anemia. The handheld device was not as accurate as the benchtop, and inaccuracies increased at lower hematocrit levels. The fingertip device was the least accurate of the three oximeters. Pulse oximeter performance is impacted by severe anemia in vitro. The use of in vitro calibration systems may play an important role in augmenting in vivo performance studies evaluating pulse oximeter performance in challenging conditions.

Frequency, Method, Intensity, and Health Sequelae of Sexual Choking Among U.S. Undergraduate and Graduate Students.

Although sexual choking is now prevalent, little is known about how people engage in choking in terms of frequency, intensity, method, or potential health sequelae. In a campus-representative survey of undergraduate and graduate students, we aimed to: (1) describe the prevalence of ever having choked/been choked as part of sex; (2) examine the characteristics of choking one's sexual partners (e.g., age at first experience, number of partners, frequency, intensity, method); (3) examine the characteristics of having been choked during sex; and (4) assess immediate responses of having been choked including the extent to which frequency and method (e.g., hand, ligature, limb) of having been choked predicts the range of responses endorsed by participants. A total of 4254 randomly sampled students (2668 undergraduate, 1576 graduate) completed a confidential online survey during Spring 2021. The mean age of first choking/being choked was about 19, with more undergraduates than graduate students reporting first choking/being choked in adolescence. Women and transgender/gender non-binary participants were significantly more likely to have been choked than men. Participants more often reported the use of hands compared to limbs or ligature. Common responses to being choked were pleasurable sensations/euphoria (81.7%), a head rush (43.8%), feeling like they could not breathe (43.0%), difficulty swallowing (38.9%), unable to speak (37.6%), and watery eyes (37.2%). About 15% had noticed neck bruising and 3% had lost consciousness from being choked. Greater frequency and intensity of being choked was associated with reports of more physical responses as was use of limb (arm, leg) or ligature.

Perioperative Normal Saline Administration and Delayed Graft Function in Patients Undergoing Kidney Transplantation: A Retrospective Cohort Study.

BACKGROUND: Perioperative normal saline administration remains common practice during kidney transplantation. The authors hypothesized that the proportion of balanced crystalloids versus normal saline administered during the perioperative period would be associated with the likelihood of delayed graft function. METHODS: The authors linked outcome data from a national transplant registry with institutional anesthesia records from 2005 to 2015. The cohort included adult living and deceased donor transplants, and recipients with or without need for dialysis before transplant. The primary exposure was the percent normal saline of the total amount of crystalloids administered perioperatively, categorized into a low (less than or equal to 30%), intermediate (greater than 30% but less than 80%), and high normal saline group (greater than or equal to 80%). The primary outcome was the incidence of delayed graft function, defined as the need for dialysis within 1 week of transplant. The authors adjusted for the following potential confounders and covariates: transplant year, total crystalloid volume, surgical duration, vasopressor infusions, and erythrocyte transfusions; recipient sex, age, body mass index, race, number of human leukocyte antigen mismatches, and dialysis vintage; and donor type, age, and sex. RESULTS: The authors analyzed 2,515 records. The incidence of delayed graft function in the low, intermediate, and high normal saline group was 15.8% (61/385), 17.5% (113/646), and 21% (311/1,484), respectively. The adjusted odds ratio (95% CI) for delayed graft function was 1.24 (0.85 to 1.81) for the intermediate and 1.55 (1.09 to 2.19) for the high normal saline group compared with the low normal saline group. For deceased donor transplants, delayed graft function in the low, intermediate, and high normal saline group was 24% (54/225 [reference]), 28.6% (99/346; adjusted odds ratio, 1.28 [0.85 to 1.93]), and 30.8% (277/901; adjusted odds ratio, 1.52 [1.05 to 2.21]); and for living donor transplants, 4.4% (7/160 [reference]), 4.7% (14/300; adjusted odds ratio, 1.15 [0.42 to 3.10]), and 5.8% (34/583; adjusted odds ratio, 1.66 [0.65 to 4.25]), respectively. CONCLUSIONS: High percent normal saline administration is associated with delayed graft function in kidney transplant recipients.

Pediatric Distraction on Induction of Anesthesia With Virtual Reality and Perioperative Anxiolysis: A Randomized Controlled Trial.

BACKGROUND: Perioperative pediatric anxiety is common and can have a negative psychological impact on children undergoing surgery and anesthesia. Studies have shown an incidence of anxiety at induction of up to 50%. Audiovisual distraction, including virtual reality (VR), is a noninvasive, nonpharmacological modality that may reduce perioperative anxiety. The goal of this study was to determine whether immersive audiovisual distraction with a VR headset during induction of general anesthesia (GA) in pediatric patients reduced preoperative anxiety. METHODS: In this randomized-controlled, parallel-group study, 71 children 5-12 years of age scheduled for elective surgery with GA were randomly allocated to a VR group or a non-VR (No VR) control group. VR group patients underwent audiovisual distraction with a VR headset during induction in the operating room, whereas the control group received no audiovisual distraction. The primary outcome was the Modified Yale Preoperative Anxiety Scale (mYPAS), which was measured at 3 time points to assess patient anxiety: in the preoperative holding area before randomization, on entering the operating room, and during induction of GA. The primary outcome was analyzed using univariate analysis and a linear mixed-effects model. Secondary outcomes included postinduction parental anxiety measured by the State-Trait Anxiety Inventory, pediatric induction compliance, and parental satisfaction. RESULTS: Average patient age was 8.0 ± 2.3 years (mean ± standard deviation [SD]), and 51.4% of patients were female. Baseline variables were not substantially different between the VR group (33 patients) and the No VR group (37 patients). No patients received preoperative anxiolytic medication. Baseline mYPAS scores were not different between the groups, with scores of 28.3 (23.3-28.3) (median [interquartile range {IQR}]) in both. The change in mYPAS scores from baseline to time of induction was significantly lower in the VR group versus control group (0.0 [0.0-5.0] vs 13.3 [5.0-26.7]; P < .0001). In the mixed-effects model, the VR group had an estimated 6.0-point lower mYPAS score (95% confidence interval [CI], 0.7-11.3; P = .03) at room entry than the No VR group, and 14.5-point lower score (95% CI, 9.3-19.8; P < .0001) at induction versus control. Randomization to VR did not alter parental anxiety (0 [-2 to 2]), pediatric induction compliance (0 [0-0]), or parental satisfaction (-3 [-8 to 2]) (difference in medians [95% CI]). CONCLUSIONS: This study demonstrates a reduction in pediatric preoperative anxiety with the use of VR. Preoperative VR may be an effective noninvasive modality for anxiolysis during induction of anesthesia in children.

Anesthesia for Maternal-Fetal Interventions: A Survey of Fetal Therapy Centers in the North American Fetal Therapy Network.

INTRODUCTION: A wide range of fetal interventions are performed across fetal therapy centers (FTCs). We hypothesized that there is significant variability in anesthesia staffing and anesthetic techniques. METHODS: We conducted an online survey of anesthesiology directors at every FTC within the North American Fetal Therapy Network (NAFTNet). The survey included details of fetal interventions performed in 2018, anesthesia staffing models, anesthetic techniques, fetal monitoring, and postoperative management. RESULTS: There was a 92% response rate. Most FTCs are located within an adult hospital and employ a small team of anesthesiologists. There is heterogeneity when evaluating anesthesiology fellowship training and staffing, indicating there is a multidisciplinary specialty team-based approach even within anesthesiology. Minimally invasive fetal interventions were the most commonly performed. The majority of FTCs also performed ex utero intrapartum treatment (EXIT) and open mid-gestation procedures under general anesthesia (GA). Compared to FTCs only performing minimally invasive procedures, FTCs performing open fetal procedures were more likely to have a pediatric surgeon as director and performed more minimally invasive procedures. CONCLUSIONS: There is considerable variability in anesthesia staffing, caseload, and anesthetic techniques among FTCs in NAFTNet. Most FTCs used maternal sedation for minimally invasive procedures and GA for EXIT and open fetal surgeries.

A Comparison of Spinal Anesthesia Versus Monitored Anesthesia Care With Local Anesthesia in Minimally Invasive Fetal Surgery.

BACKGROUND: Minimally invasive fetal surgery is commonly performed to treat twin-to-twin transfusion syndrome with selective fetoscopic laser photocoagulation and twin-reversed arterial perfusion sequence using radiofrequency ablation. Although an increasing number of centers worldwide are performing these procedures, anesthetic management varies. Both neuraxial anesthesia and monitored anesthesia care with local anesthesia are used at different institutions. We sought to determine the efficacy and outcomes of these 2 anesthetic techniques for fetal procedures at our institution. METHODS: All patients undergoing minimally invasive fetal surgery for twin-to-twin transfusion syndrome or twin-reversed arterial perfusion sequence over a 6-year time period (2011-2016) were reviewed. Patients receiving monitored anesthesia care with local anesthesia were compared with those receiving spinal anesthesia in both selective fetoscopic laser photocoagulation and radiofrequency ablation fetal procedures. The primary outcome examined between the monitored anesthesia care and spinal anesthesia groups was the difference in conversion to general anesthesia using a noninferiority design with a noninferiority margin of 5%. Secondary outcome measures included use of vasopressors, procedure times, intraoperative fluids administered, maternal complications, and unexpected fetal demise within 24 hours of surgery. RESULTS: The difference in failure rate between monitored anesthesia care and spinal was -0.5% (95% CI, -4.8% to 3.7%). Patients receiving monitored anesthesia care plus local anesthesia were significantly less likely to need vasopressors, had a shorter presurgical operating room time, and received less fluid (P < .001). Operative time did not differ significantly. CONCLUSIONS: Monitored anesthesia care plus local anesthesia is a reliable and safe anesthetic choice for minimally invasive fetal surgery. Furthermore, it decreases maternal hemodynamic instability and reduces preincision operating room time.

New Method of Destroying Waste Anesthetic Gases Using Gas-Phase Photochemistry.

BACKGROUND: The inhalation anesthetics are potent greenhouse gases. To reduce the global environmental impact of the health care sector, technologies are sought to limit the release of waste anesthetic gas into the atmosphere. METHODS: Using a photochemical exhaust gas destruction system, removal efficiencies for nitrous oxide, desflurane, and sevoflurane were measured at various inlet concentrations (25% and 50%; 1.5%, 3.0%, and 6.0%; and 0.5%, 1.0%, and 2.0%, respectively) with flow rates ranging from 0.25 to 2.0 L/min. To evaluate the economic competitiveness of the anesthetic waste gas destruction system, its price per ton of carbon dioxide equivalent was calculated and compared to other greenhouse gas abatement technologies and current market prices. RESULTS: All inhaled anesthetics evaluated demonstrate enhanced removal efficiencies with decreasing flow rates (P < .0001). Depending on the anesthetic and its concentration, the photochemical exhaust gas destruction system exhibits a constant first-order removal rate, k. However, there was not a simple relation between the removal rate k and the species concentration. The costs for removing a ton of carbon dioxide equivalents are <$0.005 for desflurane, <$0.114 for sevoflurane, and <$49 for nitrous oxide. CONCLUSIONS: Based on this prototype study, destroying sevoflurane and desflurane with this photochemical anesthetic waste gas destruction system design is efficient and cost-effective. This is likely also true for other halogenated inhalational anesthetics such as isoflurane. Due to differing chemistry of nitrous oxide, modifications of this prototype photochemical reactor system are necessary to improve its removal efficiency for this gas.

Therapeutic Hypothermia in Deceased Organ Donors and Kidney-Graft Function.

BACKGROUND: Delayed graft function, which is reported in up to 50% of kidney-transplant recipients, is associated with increased costs and diminished long-term graft function. The effect that targeted mild hypothermia in organ donors before organ recovery has on the rate of delayed graft function is unclear. METHODS: We enrolled organ donors (after declaration of death according to neurologic criteria) from two large donation service areas and randomly assigned them to one of two targeted temperature ranges: 34 to 35°C (hypothermia) or 36.5 to 37.5°C (normothermia). Temperature protocols, which were initiated after authorization was obtained for the organ to be donated and for the donor's participation in the study, ended when organ donors left the intensive care unit for organ recovery in the operating room. The primary outcome was delayed graft function in the kidney recipients, which was defined as the requirement for dialysis during the first week after transplantation. Secondary outcomes were the rates of individual organs transplanted in each treatment group and the total number of organs transplanted from each donor. RESULTS: The study was terminated early, on the recommendation of an independent data and safety monitoring board, after the interim analysis showed efficacy of hypothermia. At trial termination, 370 organ donors had been enrolled (180 in the hypothermia group and 190 in the normothermia group). A total of 572 patients received a kidney transplant (285 kidneys from donors in the hypothermia group and 287 kidneys from donors in the normothermia group). Delayed graft function developed in 79 recipients of kidneys from donors in the hypothermia group (28%) and in 112 recipients of kidneys from donors in the normothermia group (39%) (odds ratio, 0.62; 95% confidence interval, 0.43 to 0.92; P=0.02). CONCLUSIONS: Mild hypothermia, as compared with normothermia, in organ donors after declaration of death according to neurologic criteria significantly reduced the rate of delayed graft function among recipients. (Funded by the Health Resources and Services Administration; ClinicalTrials.gov number, NCT01680744.).

Effects of Changes in Arterial Carbon Dioxide and Oxygen Partial Pressures on Cerebral Oximeter Performance.

BACKGROUND: Cerebral oximetry (cerebral oxygen saturation; ScO2) is used to noninvasively monitor cerebral oxygenation. ScO2 readings are based on the fraction of reduced and oxidized hemoglobin as an indirect estimate of brain tissue oxygenation and assume a static ratio of arterial to venous intracranial blood. Conditions that alter cerebral blood flow, such as acute changes in PaCO2, may decrease accuracy. We assessed the performance of two commercial cerebral oximeters across a range of oxygen concentrations during normocapnia and hypocapnia. METHODS: Casmed FORE-SIGHT Elite (CAS Medical Systems, Inc., USA) and Covidien INVOS 5100C (Covidien, USA) oximeter sensors were placed on 12 healthy volunteers. The fractional inspired oxygen tension was varied to achieve seven steady-state levels including hypoxic and hyperoxic PaO2 values. ScO2 and simultaneous arterial and jugular venous blood gas measurements were obtained with both normocapnia and hypocapnia. Oximeter bias was calculated as the difference between the ScO2 and reference saturation using manufacturer-specified weighting ratios from the arterial and venous samples. RESULTS: FORE-SIGHT Elite bias was greater during hypocapnia as compared with normocapnia (4 ± 9% vs. 0 ± 6%; P < 0.001). The INVOS 5100C bias was also lower during normocapnia (5 ± 15% vs. 3 ± 12%; P = 0.01). Hypocapnia resulted in a significant decrease in mixed venous oxygen saturation and mixed venous oxygen tension, as well as increased oxygen extraction across fractional inspired oxygen tension levels (P < 0.0001). Bias increased significantly with increasing oxygen extraction (P < 0.0001). CONCLUSIONS: Changes in PaCO2 affect cerebral oximeter accuracy, and increased bias occurs with hypocapnia. Decreased accuracy may represent an incorrect assumption of a static arterial-venous blood fraction. Understanding cerebral oximetry limitations is especially important in patients at risk for hypoxia-induced brain injury, where PaCO2 may be purposefully altered.

Four Types of Pulse Oximeters Accurately Detect Hypoxia during Low Perfusion and Motion.

BACKGROUND: Pulse oximeter performance is degraded by motion artifacts and low perfusion. Manufacturers developed algorithms to improve instrument performance during these challenges. There have been no independent comparisons of these devices. METHODS: We evaluated the performance of four pulse oximeters (Masimo Radical-7, USA; Nihon Kohden OxyPal Neo, Japan; Nellcor N-600, USA; and Philips Intellivue MP5, USA) in 10 healthy adult volunteers. Three motions were evaluated: tapping, pseudorandom, and volunteer-generated rubbing, adjusted to produce photoplethsmogram disturbance similar to arterial pulsation amplitude. During motion, inspired gases were adjusted to achieve stable target plateaus of arterial oxygen saturation (SaO2) at 75%, 88%, and 100%. Pulse oximeter readings were compared with simultaneous arterial blood samples to calculate bias (oxygen saturation measured by pulse oximetry [SpO2] - SaO2), mean, SD, 95% limits of agreement, and root mean square error. Receiver operating characteristic curves were determined to detect mild (SaO2 < 90%) and severe (SaO2 < 80%) hypoxemia. RESULTS: Pulse oximeter readings corresponding to 190 blood samples were analyzed. All oximeters detected hypoxia but motion and low perfusion degraded performance. Three of four oximeters (Masimo, Nellcor, and Philips) had root mean square error greater than 3% for SaO2 70 to 100% during any motion, compared to a root mean square error of 1.8% for the stationary control. A low perfusion index increased error. CONCLUSIONS: All oximeters detected hypoxemia during motion and low-perfusion conditions, but motion impaired performance at all ranges, with less accuracy at lower SaO2. Lower perfusion degraded performance in all but the Nihon Kohden instrument. We conclude that different types of pulse oximeters can be similarly effective in preserving sensitivity to clinically relevant hypoxia.

Central venous pressure monitoring in living donor kidney recipients does not affect immediate graft function: A propensity score analysis.

BACKGROUND: During kidney transplantation, intraoperative fluid management can affect post-transplant graft function. It is unclear whether or not central venous pressure (CVP) monitoring is required to guide fluid therapy during kidney transplantation. METHODS: We compared post-transplant graft function in recipients of living donor kidney transplants between August 2006 and March 2009 based on the use or absence of intraoperative CVP monitoring. Graft function, assessed using the creatinine reduction ratio on postoperative day 2 (CCR2), was evaluated by multivariable linear regression analysis and in a propensity-matched cohort. RESULTS: Two hundred and ninety patients were included in the analysis. Central venous pressure was monitored in 84 patients (29%). There was no difference in post-transplant graft function, as measured by CCR2, between patients with and without CVP monitoring in both unadjusted and multivariable-adjusted analyses. There were also no statistically significant differences in CCR2, delayed graft function, or 3-month renal function between those monitored with CVP and those without, in the propensity-matched cohort. CONCLUSIONS: In this single-center analysis, immediate post-transplant renal function was not associated with the use of intraoperative CVP monitoring.

Comparison of Transcranial Doppler and Ultrasound-Tagged Near Infrared Spectroscopy for Measuring Relative Changes in Cerebral Blood Flow in Human Subjects.

BACKGROUND: Currently, no reliable method exists for continuous, noninvasive measurements of absolute cerebral blood flow (CBF). We sought to determine how changes measured by ultrasound-tagged near-infrared spectroscopy (UT-NIRS) compare with changes in CBF as measured by transcranial Doppler (TCD) in healthy volunteers during profound hypocapnia and hypercapnia. METHODS: Ten healthy volunteers were monitored with a combination of TCD, UT-NIRS (c-FLOW, Ornim Medical), as well as heart rate, blood pressure, end-tidal PCO2 (PEtCO2), end-tidal O2, and inspired O2. Inspired CO2 and minute ventilation were controlled to achieve 5 stable plateau goals of EtCO2 at 15-20, 25-30, 35-40, 45-50, and 55-60 mm Hg, for a total of 7 measurements per subject. CBF was assessed at a steady state, with the TCD designated as the reference standard. The primary analysis was a linear mixed-effect model of TCD and UT-NIRS flow with PEtCO2, which accounts for repeated measures. Receiver operating characteristic curves were determined for detection of changes in CBF. RESULTS: Hyperventilation (nadir PEtCO2 17.1 ± 2.4) resulted in significantly decreased mean flow velocity of the middle cerebral artery from baseline (to 79% ± 22%), but not a consistent decrease in UT-NIRS cerebral flow velocity index (n = 10; 101% ± 6% of baseline). Hypercapnia (peak PEtCO2 59.3 ± 3.3) resulted in a significant increase from baseline in both mean flow velocity of the middle cerebral artery (153% ± 25%) and UT-NIRS (119% ± 11%). Comparing slopes versus PEtCO2 as a percent of baseline for the TCD (1.7% [1.5%-2%]) and UT-NIRS (0.4% [0.3%-0.5%]) shows that the UT-NIRS slope is significantly flatter, P < .0001. Area under the receiver operating characteristic curve was significantly higher for the TCD than for UT-NIRS, 0.97 (95% confidence interval, 0.92-0.99) versus 0.75 (95% confidence interval, 0.66-0.82). CONCLUSIONS: Our data indicate that UT-NIRS cerebral flow velocity index detects changes in CBF only during hypercarbia but not hypocarbia in healthy subjects and with much less sensitivity than TCD. Additional refinement and validation are needed before widespread clinical utilization of UT-NIRS.

Incidence and Management of Umbilical Artery Flow Abnormalities during Open Fetal Surgery.

INTRODUCTION: Umbilical artery (UA) Doppler ultrasound is used to assess uteroplacental insufficiency. Absent or reversed end diastolic flow (AREDF) in the UA is associated with increased perinatal mortality in fetuses with intrauterine growth restriction. We describe the incidence of UA Doppler abnormalities during open fetal surgery. METHODS: We conducted a retrospective review of patients undergoing open in utero myelomeningocele (MMC) repair between 2008 and 2015. Intermittent UA Dopplers were performed during key portions of all cases. Our primary outcome was the rate of any AREDF. Secondary outcomes included analysis of absent versus reversed end diastolic flow (EDF), vasopressor use, and volatile anesthetic and clinical outcomes. RESULTS: Thirty-four of 47 fetuses developed UA Doppler abnormalities intraoperatively. Nineteen had absent EDF and 15 had reversed EDF. No AREDF was present before induction, and all AREDF resolved by postoperative day 1. Ten of 19 (52.6%) patients who received sevoflurane had reversed EDF, versus 5/28 (17.9%) for desflurane, odds ratio (95% CI) 5.11 (1.36-19.16), p = 0.02. One intraoperative fetal death occurred in the AREDF group. DISCUSSION: AREDF is a common phenomenon during open MMC repair. Anesthetic agent choice may influence this risk. Future studies of UA flow during fetal surgery are needed to further evaluate the impact of intraoperative AREDF on fetal well-being.

Changes in transcranial motor evoked potentials during hemorrhage are associated with increased serum propofol concentrations.

Transcranial motor evoked potentials (TcMEPs) monitor the integrity of the spinal cord during spine surgery. Propofol-based anesthesia is favored in order to enhance TcMEP quality. During intraoperative hemorrhage, TcMEP amplitudes may be reduced. The serum concentration of propofol may increase during hemorrhage. No study has determined whether changes in TcMEPs due to hemorrhage are related to changes in propofol blood levels. We monitored TcMEPs, mean arterial pressure (MAP), and cardiac output (CO) and hemoglobin in pigs (n = 6) undergoing controlled progressive hemorrhage during a standardized anesthetic with infusions of propofol, ketamine, and fentanyl. We recorded TcMEPs from the rectus femoris (RF) and tibialis anterior (TA) muscles bilaterally. A pulmonary artery catheter was placed to measure CO. Progressive hemorrhage of 10% blood volume increments was done until TcMEP amplitude decreased by >60% from baseline. Serum propofol levels were also measured following removal of each 10% blood volume increment. TcMEP responses were elicited every 3 min using constant stimulation parameters. We removed between 20 and 50% of total blood volume in order to achieve the >60% reduction in TcMEP amplitude. MAP and CO decreased significantly from baseline. At maximum hemorrhage, TcMEP amplitude decreased in the RF and TA by an average of 73 and 62% respectively from baseline (P < 0.01). Serum propofol levels varied greatly among animals at baseline (range 410-1720 ng/mL) and increased in each animal during hemorrhage. The mean propofol concentration rose from 1190 ± 530 to 2483 ± 968 ng/mL (P < 0.01). The increased propofol concentration correlated with decreased CO. Multivariate analysis using hierarchical linear models indicated that the decline of TcMEP amplitude was primarily associated with rising propofol concentrations, but was also independently affected by reduced CO. We believe that the decrease in blood volume and CO during hemorrhage increased the serum concentration of propofol by reducing the volume of distribution and/or rate of hepatic metabolism of the drug. Despite wide acceptance of propofol as the preferred anesthetic when using TcMEPs, intravenous anesthetics are vulnerable to altered pharmacokinetics during conditions of hemorrhage and could contribute to false-positive TcMEP changes.

Correction to: Changes in transcranial motor evoked potentials during hemorrhage are associated with increased serum propofol concentrations.

In the original publication of the article, the corresponding author inadvertently omitted one of the co-authors in the author group. The corrected author group is given in this erratum.

Evaluating Pulmonary Function: An Assessment of PaO2/FIO2.

OBJECTIVES: PaO2/FIO2 is used commonly for diagnosis of lung injury (acute respiratory distress syndrome and transfusion-related acute lung injury), for assessment of pulmonary disease course and therapy, and in pulmonary transplantation for evaluation of donor lungs and clinical outcome. It was developed for convenience, without formal mathematical and graphic assessment to validate its suitability for these purposes. DESIGN: We examined, mathematically and graphically, the relationship of PaO2/FIO2 to FIO2 at constant normal and several degrees of increased intrapulmonary shunting (QS/QT), assessing the impact of intra- and extrapulmonary factors on the relationship and thus the reliability of PaO2/FIO2. MEASUREMENTS AND MAIN RESULTS: The relationship of PaO2/FIO2 varies at all shunt fractions but most with QS/QT from 0.1 to 0.3 with FIO2 approximately greater than 0.4. At higher QS/QT, the relationship is more constant and changes less with FIO2 more than 0.4. Hemoglobin concentration and arterial-venous oxygen content difference have large effects that can confound interpretation of PaO2/FIO2. Barometric pressure has a substantial effect; PCO2, base excess, and respiratory quotient have small effects. CONCLUSIONS: At high QS/QT with FIO2 more than 0.4, the relationship of PaO2/FIO2 to FIO2 is relatively constant. However, with QS/QT of 0.1-0.3, PaO2/FIO2 changes substantially with FIO2. Understanding the important effects of nonpulmonary factors (especially hemoglobin concentration and arterial-venous oxygen content difference) should enhance appropriate clinical use, interpretation of PaO2/FIO2, and interpretation of previous publications and future studies (especially those seeking to assess effects of anemia or transfusion on lung function). The ratio of PaO2/FIO2 is a good tool for some, but not many clinical circumstances, and is insufficiently robust for most research applications.

Tissue Oximetry and Clinical Outcomes.

A number of different technologies have been developed to measure tissue oxygenation, with the goal of identifying tissue hypoxia and guiding therapy to prevent patient harm. In specific cases, tissue oximetry may provide clear indications of decreases in tissue oxygenation such as that occurring during acute brain ischemia. However, the causation between tissue hemoglobin-oxygen desaturation in one organ (eg, brain or muscle) and global outcomes such as mortality, intensive care unit length of stay, and remote organ dysfunction remains more speculative. In this review, we describe the current state of evidence for predicting clinical outcomes from tissue oximetry and identify several issues that need to be addressed to clarify the link between tissue oxygenation and outcomes. We focus primarily on the expanding use of near-infrared spectroscopy to assess a venous-weighted mixture of venous and arterial hemoglobin-oxygen saturation deep in tissues such as brain and muscle. Our analysis finds that more work is needed in several areas: establishing threshold prediction values for tissue desaturation-related injury in specific organs, defining the types of interventions required to correct changes in tissue oxygenation, and defining the effect of interventions on outcomes. Furthermore, well-designed prospective studies that test the hypothesis that monitoring oxygenation status in one organ predicts outcomes related to other organs need to be done. Finally, we call for more work that defines regional variations in tissue oxygenation and improves technology for measuring and even imaging oxygenation status in critical organs. Such studies will contribute to establishing that monitoring and imaging of tissue oxygenation will become routine in the care of high-risk patients because the monitors will provide outputs that direct therapy to improve clinical outcomes.

Effects of Acute, Profound Hypoxia on Healthy Humans: Implications for Safety of Tests Evaluating Pulse Oximetry or Tissue Oximetry Performance.

Extended periods of oxygen deprivation can produce acidosis, inflammation, energy failure, cell stress, or cell death. However, brief profound hypoxia (here defined as SaO2 50%-70% for approximately 10 minutes) is not associated with cardiovascular compromise and is tolerated by healthy humans without apparent ill effects. In contrast, chronic hypoxia induces a suite of adaptations and stresses that can result in either increased tolerance of hypoxia or disease, as in adaptation to altitude or in the syndrome of chronic mountain sickness. In healthy humans, brief profound hypoxia produces increased minute ventilation and increased cardiac output, but little or no alteration in blood chemistry. Central nervous system effects of acute profound hypoxia include transiently decreased cognitive performance, based on alterations in attention brought about by interruptions of frontal/central cerebral connectivity. However, provided there is no decrease in cardiac output or ischemia, brief profound hypoxemia in healthy humans is well tolerated without evidence of acidosis or lasting cognitive impairment.