Keita Ikeda

Regional brain blood flow in man during acute changes in arterial blood gases

•  The partial pressures of arterial carbon dioxide () and oxygen () has a marked influence on brain blood flow. •  It is unclear if the larger brain arteries are also sensitive to changing and and if different areas of the brain possess different sensitivities. •  We separately altered and and measured the diameter and blood flow in the main arteries delivering blood to the cortex and brainstem. •  During alterations in and , the large arteries changed diameter and blood flow to the brainstem changed more than that to the cortex. •  These findings change the basis of our understanding of brain blood flow control in humans.

Consensus Statements Regarding the Multidisciplinary Care of Limb Amputation Patients in Disasters or Humanitarian Emergencies: Report of the 2011 Humanitarian Action Summit Surgical Working Group on Amputations Following Disasters or Conflict

Limb amputations are frequently performed as a result of trauma inflicted during conflict or disasters. As demonstrated during the 2010 earthquake in Haiti, coordinating care of these patients in austere settings is complex. During the 2011 Humanitarian Action Summit, consensus statements were developed for international organizations providing care to limb amputation patients during disasters or humanitarian emergencies. Expanded planning is needed for a multidisciplinary surgical care team, inclusive of surgeons, anesthesiologists, rehabilitation specialists and mental health professionals. Surgical providers should approach amputation using an operative technique that optimizes limb length and prosthetic fitting. Appropriate anesthesia care involves both peri-operative and long-term pain control. Rehabilitation specialists must be involved early in treatment, ideally before amputation, and should educate the surgical team in prosthetic considerations. Mental health specialists must be included to help the patient with community reintegration. A key step in developing local health systems the establishment of surgical outcomes monitoring. Such monitoring can optimizepatient follow-up and foster professional accountability for the treatment of amputation patients in disaster settings and humanitarian emergencies.

The Accuracy of a Near-Infrared Spectroscopy Cerebral Oximetry Device and Its Potential Value for Estimating Jugular Venous Oxygen Saturation

BACKGROUND:An intriguing potential clinical use of cerebral oximeter measurements (SctO2) is the ability to noninvasively estimate jugular bulb venous oxygen saturation (SjvO2). Our purpose in this study was to determine the accuracy of the FORE-SIGHT® (CAS Medical Systems, Branford, CT), which is calibrated to a weighted average of 70% (SjvO2) and 30% arterial saturation, for Food and Drug Administration pre-market approval 510(k) certification by adapting an industry standard protocol, ISO 9919:2005 (www.ISO.org) (used for pulse oximeters), and to evaluate the use of SctO2 and SpO2 measurements to noninvasively estimate jugular venous oxygen saturation (SnvO2). METHODS:Paired blood gas samples from the radial artery and the jugular venous bulb were collected from 20 healthy volunteers undergoing progressive oxygen desaturation from 100% to 70%. The blood sample pairs were analyzed via co-oximetry and used to calculate the approximate mixed vascular cerebral blood oxygen saturation, or reference SctO2 values (refSctO2), during increasing hypoxia. These reference values were compared to bilateral FORE-SIGHT SctO2 values recorded simultaneously with the blood gas draws to determine its accuracy. Bilateral SctO2 and SpO2 measurements were then used to calculate SnvO2 values which were compared to SjvO2. RESULTS:Two hundred forty-six arterial and 253 venous samples from 18 subjects were used in the analysis. The ipsilateral FORE-SIGHT SctO2 values showed a tolerance interval (TI) of [−10.72 to 10.90] and Lin concordance correlation coefficient (CCC) with standard error (SE) of 0.83 ± 0.073 with the refSctO2 values calculated using arterial and venous blood gases. The ipsilateral data had a CCC of 0.81 + 0.059 with TI of [−9.22 to 9.40] with overall bias of 0.09%, and amplitude of the root mean square of error after it was corrected with random effects analysis was 2.92%. The bias and variability values between the ipsilateral and the contralateral FORE-SIGHT SctO2 measurements varied from person to person. The SnvO2 calculated from the ipsilateral SctO2 and SpO2 data showed a CCC ± SE of 0.79 ± 0.088, TI = [−14.93 to 15.33], slope of 0.98, y-intercept of 1.14% with SjvO2 values with a bias of 0.20% and an Arms of 4.08%. The SnvO2 values calculated independently from contralateral forehead FORE-SIGHT SctO2 values were not as correlated with the SjvO2 values (contralateral side CCC + SE = 0.72 ± 0.118, TI = [−14.86 to 15.20], slope of 0.66, and y-intercept of 20.36%). CONCLUSIONS:The FORE-SIGHT cerebral oximeter was able to estimate oxygen saturation within the tissues of the frontal lobe under conditions of normocapnia and varying degrees of hypoxia (with 95% confidence interval of [−5.60 to 5.78] with ipsilateral blood sample data). These findings from healthy volunteers also suggest that the use of the calculated SnvO2 derived from SctO2 and SpO2 values may be a reasonable noninvasive method of estimating SjvO2 and therefore global cerebral oxygen consumption in the clinical setting. Further laboratory and clinical research is required to define the clinical utility of near-infrared spectroscopy determination of SctO2 and SnvO2 in the operating room setting.

Influence of high altitude on cerebral blood flow and fuel utilization during exercise and recovery

This study assessed the dynamic response of global cerebral blood flow (CBF) and cerebral fuel utilization during and following incremental supine exercise to exhaustion. Global CBF increased more during exercise and recovery at high altitude (HA) compared with sea level (SL) such that cerebral oxygen delivery ( CDO2 ) was maintained. The increase in cerebral metabolic rate of oxygen during maximal exercise at HA was half the increase observed at SL. Arterial lactate production during exercise at the same absolute intensities was greater at HA compared with SL, but reduced at the same relative intensities. Cerebral carbohydrate uptake (lactate and glucose) is greater than oxygen uptake at HA compared with SL, indicating a shift towards an increased non‐oxidative metabolic utilization. These results suggest that CBF increases to maintain CDO2 during exercise at HA while changes in arterial lactate concentration and exercise intensity augment the oxidative and non‐oxidative pathways to cerebral metabolism at HA.

Best Practice Guidelines on Surgical Response in Disasters and Humanitarian Emergencies: Report of the 2011 Humanitarian Action Summit Working Group on Surgical Issues within the Humanitarian Space

The provision of surgery within humanitarian crises is complex, requiring coordination and cooperation among all stakeholders. During the 2011 Humanitarian Action Summit best practice guidelines were proposed to provide greater accountability and standardization in surgical humanitarian relief efforts. Surgical humanitarian relief planning should occur early and include team selection and preparation, appropriate disaster-specific anticipatory planning, needs assessment, and an awareness of local resources and limitations of cross-cultural project management. Accurate medical record keeping and timely follow-up is important for a transient surgical population. Integration with local health systems is essential and will help facilitate longer term surgical health system strengthening.

Development and Validation of a Cerebral Oximeter Capable of Absolute Accuracy

OBJECTIVE Cerebral oximetry may be a valuable monitor, but few validation data are available, and most report the change from baseline rather than absolute accuracy, which may be affected by individuals whose oximetric values are outside the expected range. The authors sought to develop and validate a cerebral oximeter capable of absolute accuracy. DESIGN An in vivo research study. SETTING A university human physiology laboratory. PARTICIPANTS Healthy human volunteers were enrolled in calibration and validation studies of 2 cerebral oximetric sensors, the Nonin 8000CA and 8004CA. The 8000CA validation study identified 5 individuals with atypical cerebral oxygenation values; their data were used to design the 8004CA sensor, which subsequently underwent calibration and validation. INTERVENTIONS Volunteers were taken through a stepwise hypoxia protocol to a minimum saturation of peripheral oxygen. Arteriovenous saturation (70% jugular bulb venous saturation and 30% arterial saturation) at 6 hypoxic plateaus was used as the reference value for the cerebral oximeter. Absolute accuracy was defined using a combination of the bias and precision of the paired saturations (A(RMS)). MEASUREMENTS AND MAIN RESULTS In the validation study for the 8000CA sensor (n = 9, 106 plateaus), relative accuracy was an A(RMS) of 2.7, with an absolute accuracy of 8.1, meeting the criteria for a relative (trend) monitor, but not an absolute monitor. In the validation study for the 8004CA sensor (n = 11, 119 plateaus), the A(RMS) of the 8004CA was 4.1, meeting the prespecified success criterion of <5.0. CONCLUSIONS The Nonin cerebral oximeter using the 8004CA sensor can provide absolute data on regional cerebral saturation compared with arteriovenous saturation, even in subjects previously shown to have values outside the normal population distribution curves.

Inhaled fentanyl aerosol in healthy volunteers: pharmacokinetics and pharmacodynamics.

BACKGROUND:Rapid delivery of potent opioid to the systemic circulation is an important feature for the effective treatment of acute and acute-on-chronic breakthrough pain. The delivery of different opioids by the pulmonary route has been inconsistent, usually resulting in low bioavailability of the drug. Staccato® Fentanyl for Inhalation is a handheld inhaler producing a single metered dose of aerosolized fentanyl during a single inspiration. The aerosol is of high purity (≥98%) at a particle size (1 to 3.5 microns) shown to be best for pulmonary absorption. METHODS:We conducted the study in healthy volunteers in 2 stages. In the crossover stage, 10 subjects received IV fentanyl 25 µg and inhaled fentanyl 25 µg on separate occasions. The dose escalation stage was a multidose, randomized, double-blind, placebo-controlled, single-period dose escalation study of inhaled fentanyl (50 to 300 µg). Serial blood sampling was performed over an 8-hour period after drug administration to determine the pharmacokinetic profile, and serial pupillometry was performed as a measure of pharmacodynamic effect. RESULTS:In the crossover stage the pharmacokinetic profiles of the inhaled and IV fentanyl showed similar peak arterial concentrations and areas under the curve. The time to maximum concentration was slightly shorter for the inhaled than IV fentanyl, 20.5 and 31.5 seconds, respectively. In the dose escalation stage the administration of repeated doses resulted in predictable, dose-dependent serum concentrations. CONCLUSIONS:This study has demonstrated that the pharmacokinetic profile of single doses of inhaled fentanyl is comparable to IV administration.

Accuracy of the Lifebox pulse oximeter during hypoxia in healthy volunteers

Pulse oximetry is a standard of care during anaesthesia in high‐income countries. However, 70% of operating environments in low‐ and middle‐income countries have no pulse oximeter. The ‘Lifebox’ oximetry project set out to bridge this gap with an inexpensive oximeter meeting CE (European Conformity) and ISO (International Organization for Standardization) standards. To date, there are no performance‐specific accuracy data on this instrument. The aim of this study was to establish whether the Lifebox pulse oximeter provides clinically reliable haemoglobin oxygen saturation (SpO2) readings meeting USA Food and Drug Administration 510(k) standards. Using healthy volunteers, inspired oxygen fraction was adjusted to produce arterial haemoglobin oxygen saturation (SaO2) readings between 71% and 100% measured with a multi‐wavelength oximeter. Lifebox accuracy was expressed using bias (SpO2 − SaO2), precision (SD of the bias) and the root mean square error (Arms). Simultaneous readings of SaO2 and SpO2 in 57 subjects showed a mean (SD) bias of −0.41% (2.28%) and Arms 2.31%. The Lifebox pulse oximeter meets current USA Food and Drug Administration standards for accuracy, thus representing an inexpensive solution for patient monitoring without compromising standards.

The contribution of arterial blood gases in cerebral blood flow regulation and fuel utilization in man at high altitude.

The effects of partial acclimatization to high altitude (HA; 5,050 m) on cerebral metabolism and cerebrovascular function have not been characterized. We hypothesized (1) increased cerebrovascular reactivity (CVR) at HA; and (2) that CO2 would affect cerebral metabolism more than hypoxia. PaO2 and PaCO2 were manipulated at sea level (SL) to simulate HA exposure, and at HA, SL blood gases were simulated; CVR was assessed at both altitudes. Arterial–jugular venous differences were measured to calculate cerebral metabolic rates and cerebral blood flow (CBF). We observed that (1) partial acclimatization yields a steeper CO2-H+ relation in both arterial and jugular venous blood; yet (2) CVR did not change, despite (3) mean arterial pressure (MAP)-CO2 reactivity being doubled at HA, thus indicating effective cerebral autoregulation. (4) At SL hypoxia increased CBF, and restoration of oxygen at HA reduced CBF, but neither had any effect on cerebral metabolism. Acclimatization resets the cerebrovasculature to chronic hypocapnia.

Real-Time Doppler-Based Arterial Vascular Impedance and Peripheral Pressure-Flow Loops: A Pilot Study

OBJECTIVE Arterial pressure-flow loops and vascular impedance provide additional data that could be used to assess the hemodynamic effects of therapeutic interventions in anesthetized patients. To evaluate the utility of such an approach, the authors sought to design a device that combines flow waveforms from an esophageal Doppler probe and pressure waveforms from a peripheral artery to produce real-time pressure-flow loops and estimates of arterial vascular impedance. DESIGN Prospective, cohort study. SETTING Single center, university-based teaching hospital. PARTICIPANTS Patients undergoing surgery in whom the attending anesthesiologist had opted to place an esophageal Doppler probe and a peripheral arterial catheter for hemodynamic monitoring. INTERVENTIONS This was a non-interventional study designed to record pressure-flow loops and arterial vascular impedance intraoperatively using a novel, noninvasive device. MEASUREMENTS AND MAIN RESULTS Pressure-flow loops and arterial vascular impedance were measured noninvasively using radial artery pressure and descending thoracic aorta flow waveforms in real time. CONCLUSIONS Real-time arterial vascular impedance and peripheral pressure-volume loops can be determined using available monitoring devices. Technical feasibility of this technology in patients is a crucial first step to permit meaningful evaluation of the clinical value of this approach for accurate determination of complex hemodynamic indices and, eventually, improvement of outcomes.