Donald J. Deyo

Validation in Volunteers of a Near-infrared Spectroscope for Monitoring Brain Oxygenation In Vivo

Cerebral oximeters based on near-infrared spectroscopy may provide a continuous, noninvasive assessment of cerebral oxygenation. We evaluated a prototype cerebral oximeter (Invos 3100; Somanetics, Troy, MI) in 22 conscious, healthy volunteers breathing hypoxic gas mixtures. Using the first 12 subjects (training group), we developed an algorithm based on the mathematic relationship that converts detected light from the field surveyed by the probe to cerebral hemoglobin oxygen saturation (CSf O2). To develop the algorithm, we correlated the oximeter result with the estimated combined brain hemoglobin oxygen saturation (CScomb O2, where CScomb O2 = Sa O2 times 0.25 + Cj O2 times 0.75 and Sj O2 = jugular venous saturation). We then validated the algorithm in the remaining 10 volunteers (validation group). A close association (r2 = 0.798-0.987 for individuals in the training group and r2 = 0.794-0.992 for individuals in the validation group) existed between CSf O2 and CScomb O2. We conclude that continuous monitoring with cerebral oximetry may accurately recognize decreasing cerebral hemoglobin oxygen saturation produced by systemic hypoxemia. (Anesth Analg 1996;82:269-77)

Optoacoustic technique for noninvasive monitoring of blood oxygenation: a feasibility study

Replacement of invasive monitoring of cerebral venous oxygenation with noninvasive techniques offers great promise in the management of life-threatening neurologic illnesses including traumatic brain injury. We developed and built an optoacoustic system to noninvasively monitor cerebral venous oxygenation; the system includes a nanosecond Nd:YAG laser and a specially designed optoacoustic probe. We tested the system in vitro in sheep blood with experimentally varied oxygenation. Our results demonstrated that (1) the amplitude and temporal profile of the optoacoustic waves increase with blood oxygenation in the range from 24% to 92%, (2) optoacoustic signals can be detected despite optical and acoustic attenuation by thick bone, and (3) the system is capable of real-time and continuous measurements. These results suggest that the optoacoustic technique is technically feasible for continuous, noninvasive monitoring of cerebral venous oxygenation.

Regional Perfusion Abnormalities With Phenylephrine During Normothermic Bypass

BACKGROUND Hypotension and vasopressors during cardiopulmonary bypass may contribute to splanchnic ischemia. The effect of restoring aortic pressure on visceral organ, brain, and femoral muscle perfusion during cardiopulmonary bypass by increasing pump flow or infusing phenylephrine was examined. METHODS Twelve anesthetized swine were stabilized on normothermic cardiopulmonary bypass. After baseline measurements, including regional blood flow (radioactive microspheres), aortic pressure was reduced to 40 mm Hg by decreasing the pump flow. Next, aortic pressure was restored to 65 mm Hg either by increasing the pump flow or by titrating phenylephrine. The animals had both interventions in random order. RESULTS At 40 mm Hg aortic pressure, perfusion to all visceral organs and femoral muscle, but not to the brain, was significantly reduced. Increasing pump flow improved perfusion to the pancreas, colon, and kidneys. In contrast, infusing phenylephrine (2.4 +/- 0.6 micrograms.kg-1.min-1) increased aortic pressure but failed to improve splanchnic perfusion, so that significant perfusion differences existed between the pump flow and phenylephrine intervals. CONCLUSIONS Increasing systemic pressure during cardiopulmonary bypass with phenylephrine causes significantly lower values of splanchnic blood flow than does increasing the pump flow. Administering vasoconstrictors during normothermic cardiopulmonary bypass may mask substantial hypoperfusion of splanchnic organs despite restoration of perfusion pressure.

The influence of carbon dioxide and body position on near-infrared spectroscopic assessment of cerebral hemoglobin oxygen saturation.

Near-infrared spectroscopy may allow continuous and noninvasive monitoring of regional brain hemoglobin oxygen saturation by measuring the differential absorption of infrared light by oxyhemoglobin and deoxyhemoglobin. We have previously examined the correlation between the spectroscopic signal generated by a prototype cerebral oximeter (Invos 3100 Registered Trademark; Somanetics, Troy, MI), and global brain hemoglobin oxygen saturation calculated from arterial and jugular venous bulb oxygen saturations. Because the technology does not distinguish between arterial and venous hemoglobin saturation, changes in the proportion of cerebral arterial and venous blood volume, which may result from changes in blood flow or venous distending pressure, may confound measurements. In eight conscious volunteers breathing hypoxic oxygen mixtures, we examined the influence of supine, 20 degrees Trendeleburg, and 20 degrees reverse Trendelenburg positions on the correlation of the spectroscopic measurement of cerebral oxygen saturation in the field assessed by the probe (CSf O2) and the calculated brain hemoglobin oxygen saturation (CScomb O2), estimated as 0.25 times arterial saturation plus 0.75 times jugular venous bulb oxygen saturation. We found that changes in position did not influence the association between CSf O2 and CScomb O2 (r2 = 0.69-0.885) during hypoxic challenge. In a second set of eight volunteers, we studied the influence of hypercapnia and hypocapnia and body position on the association between CSf O2 and CScomb O2, and found that they were less well correlated (r2 = 0.366-0.976) in individual patients. Because changes in body position and PaCO2 confound the relationship between CSf O2 and CScomb O2, changes in CS (f) O2 can best be assessed if position and PaCO2 are constant. (Anesth Analg 1996;82:278-87)

Hypotensive Resuscitation Of Multiple Hemorrhages Using Crystalloid And Colloids

Hypotensive resuscitation has been advocated as a better means to perform field resuscitation of penetrating trauma. Our hypothesis is that hypotensive resuscitation using either crystalloid or colloid provides equivalent or improved metabolic function while reducing the overall fluid requirement for resuscitation of hemorrhage. We compared hypotensive and normotensive resuscitation of hemorrhage using lactated Ringer’s (LR) with hypotensive resuscitation using Hextend™ (Hex), 6% hetastarch in isotonic buffered saline. Instrumented conscious sheep were hemorrhaged in three separate bleeds, 25 mL/kg at T0 and 5 mL/kg at both T50 and T70. Resuscitation was started at T30 and continued until T180. Hypotensive resuscitation to a mean arterial pressure (MAP) of 65 mmHg was performed with LR or Hex using a closed-loop resuscitation (CLR) system for a LR-65 and Hex-65 treatment protocol. A control treatment protocol was resuscitation with LR to a MAP target of 90 mmHg, LR-90. All treatment protocols were successfully resuscitated to near target levels. Two animals in the hypotensive treatment protocols died during the second and third bleedings, one in the LR-65 and one in the Hex-65 treatment protocol. Mean infused volumes were 61.4 ± 11.3, 18.0 ± 5.9,* and 11.6 ± 1.9* mL/kg in the LR-90, LR-65, and Hex-65 treatments, respectively (*P < 0.05 versus LR-90). Mean minimum base excess (BE) values were +1.9 ± 1.4, −5.8 ± 4.3, and −5.9 ± 4.0 mEq/L in the LR-90, LR-65, and Hex-65 treatments, respectively. Hypotensive resuscitation with LR greatly reduced volume requirements as compared with normotensive resuscitation, and Hex achieved additional volume sparing. However, trends toward lower BE values and the occurrence of deaths only in the hypotensive treatment protocols suggest that resuscitation to a target MAP of 65 mmHg may be too low for optimal outcomes.

Hemodynamic and cardiac contractile function during sepsis caused by cecal ligation and puncture in mice

Sepsis is among the leading causes of death in the critically ill, yet the pathophysiology of sepsis is incompletely understood. Genetically engineered mice offer a unique opportunity to explore the cellular and molecular pathogenesis of sepsis. However, the hemodynamic responses of mice during sepsis are not completely understood because of the difficulty in performing cardiovascular measurements in mice. We used a 1.4-F pressure and conductance catheter to measure hemodynamics in wild-type C57BL/6J mice during sepsis caused by cecal ligation and puncture. Septic mice exhibited significant hypothermia compared with the sham group. In addition, there was a progressive decrease in mean arterial blood pressure and systemic vascular resistance in septic mice as well as an increase in stroke volume and cardiac output. Sepsis also caused a significant time-dependent impairment of left ventricular function as indicated by decreased dp/dtmax and dp/dtmin. The slope of end systolic pressure volume relationship also decreased over time, as did the time varying maximum elastance and preload-recruitable stroke work of the left ventricle. In conclusion, septic mice exhibit hemodynamic alterations during sepsis that are similar to those observed in humans. The miniaturized conductance catheter allows for effective measurements of hemodynamic function in septic mice and provides measurements that cannot be obtained using other cardiovascular monitoring techniques.

New clinically relevant sheep model of severe respiratory failure secondary to combined smoke inhalation/cutaneous flame burn injury.

Objectives: To develop a predictable, dose‐dependent, clinically relevant model of severe respiratory failure associated with a 40% total body surface area, full‐thickness (third‐degree) cutaneous flame burn and smoke inhalation injury in adult sheep. Design: Model development. Setting: Research laboratory. Subjects: Adult female sheep (n = 22). Interventions: Animals were divided into three groups, determined by the number of smoke breaths administered (24, 36, 48) for a graded inhalation injury. The smoke was insufflated into a tracheostomy with a modified bee smoker at airway temperatures <40°C. All animals concurrently received a 40% total body surface area (third‐degree) cutaneous flame burn to the body (flanks). After injury, the animals were placed on volume‐controlled ventilation to achieve PaO2 >60 mm Hg and PaCO2 <40 mm Hg. Arterial blood gases and ventilator settings were monitored every 6 hrs postinjury for up to 7 days. Measurements and Main Results: All animals survived the induction of injury. In the 24 smoke breath/40% total body surface area burn (24/40) group, PaO2/FIO2 never decreased below 300, and peak inspiratory pressure was consistently <14 cm H2O with normal arterial blood gases throughout the observation period. With 36 smoke breaths/40% total body surface area burn (36/40) (n = 7), all animals had PaO2/FIO2 of <200 and peak inspiratory pressure of 26 cm H2O within 40‐48 hrs, as 30% died during the study period. With 48 smoke breaths/40% total body surface area burn (48/40) (n = 12), all animals developed respiratory distress syndrome (RDS) in 24‐30 hrs, but none survived the experimental period. Conclusions: Development of RDS by smoke and cutaneous flame burn injury depends on smoke inhalation dose. A combination of 36 breaths of smoke and a 40% total body surface area (third‐degree) cutaneous flame burn injury can induce severe RDS (PaO2/FIO2 <200) within 40‐48 hrs to allow evaluation of various treatment modalities of RDS.

Continuous, noninvasive monitoring of total hemoglobin concentration by an optoacoustic technique

Measurement of total hemoglobin concentration [Hgb] is a blood test that is widely used to evaluate outpatients, hospital inpatients, and surgical patients, especially those undergoing surgery associated with extensive blood loss, rapid fluid administration, and transfusion of packed red blood cells. Current techniques for measurement of [Hgb] are invasive (requiring blood sampling) and cannot provide real-time, continuous monitoring. We propose to use an optoacoustic technique for noninvasive and continuous monitoring of [Hgb]. The high resolution of the optoacoustic technique may provide accurate measurement of [Hgb] by detection and analysis of optoacoustic signals induced by short optical pulses in blood circulating in arteries or veins. We designed, built, and tested in vitro (in both tissue phantoms and in preliminary in vivo experiments) a portable optoacoustic system for the monitoring of [Hgb] in the radial artery. The system includes a nanosecond laser operating in the near-infrared spectral range and a sensitive optoacoustic probe designed to irradiate the radial artery through the skin and detect optoacoustic signals induced in blood. Results of our studies demonstrated that (1) the slope of optoacoustic waves induced in blood in the transmission mode is linearly dependent on [Hgb] in the range from 6.2 to 12.4 g/dl, (2) optoacoustic signals can be detected despite optical attenuation in turbid tissue phantoms with a thickness of 1 cm, and (3) the optoacoustic system detects signals induced in blood circulating in the radial artery. These data suggest that the optoacoustic system can be used for accurate, noninvasive, real-time, and continuous monitoring of [Hgb].

Optoacoustic monitoring of blood hemoglobin concentration: a pilot clinical study

The optoacoustic technique is noninvasive, has high spatial resolution, and potentially can be used to measure the total hemoglobin concentration ([THb]) continuously and accurately. We performed in vitro measurements in blood and in vivo tests in healthy volunteers. Our clinical protocol included rapid infusion of intravenous saline to simulate rapid change in the [THb] during fluid therapy or surgery. Optoacoustic measurements were made from the wrist area overlying the radial artery for more than 1 h. The amplitude of the optoacoustic signal generated in the radial artery closely followed the [THb] measured directly in concurrently collected blood samples.

Increasing organ blood flow during cardiopulmonary bypass in pigs : comparison of dopamine and perfusion pressure

OBJECTIVE To determine whether low-dose dopamine infusion (5 micrograms/kg/min) during cardiopulmonary bypass selectively increases perfusion to the kidney, splanchnic organs, and brain at low (45 mm Hg) as well as high (90 mm Hg) perfusion pressures. DESIGN Randomized crossover trial. SETTING Animal research laboratory in a university medical center. SUBJECTS Ten female Yorkshire pigs (weight 29.9 +/- 1.2 kg). INTERVENTION Anesthetized pigs were placed on normothermic cardiopulmonary bypass at a 100-mL/kg/min flow rate. After baseline measurements, the animal was subjected, in random sequence, to 15-min periods of low perfusion pressure (45 mm Hg), low perfusion pressure with dopamine (5 micrograms/kg/min), high perfusion pressure (90 mm Hg), and high perfusion pressure with dopamine. Regional perfusion (radioactive microspheres) was measured in tissue samples (2 to 10 g) from the renal cortex (outer two-third and inner one-third segments), stomach, duodenum, jejunum, ileum, colon, pancreas, and cerebral hemispheres. MEASUREMENTS AND MAIN RESULTS Systemic perfusion pressure was altered by adjusting pump flow rate (r2 = .61; p < .05). In the kidney, cortical perfusion pressure increased from 178 +/- 16 mL/min/100 g at the low perfusion pressure to 399 +/- 23 mL/min/100 g at the high perfusion pressure (p < .05). Perfusion pressure augmentation increased the ratio of outer/inner renal cortical blood flow from 0.9 +/- 0.1 to 1.2 +/- 0.1 (p < .05). At each perfusion pressure, low-dose dopamine had no beneficial effect on renal perfusion or flow distribution. Similar results were found in the splanchnic organs, where regional perfusion was altered by perfusion pressure but not by dopamine. In contrast, neither changing perfusion pressure nor adding low-dose dopamine altered blood flow to the cerebral cortex. CONCLUSIONS These data indicate that the lower autoregulatory limits of perfusion to the kidneys and splanchnic organs differ from those limits to the brain during normothermic bypass. Selective vasodilation from low-dose dopamine was not found in renal, splanchnic, or cerebral vascular beds. Increasing the perfusion pressure by pump flow, rather than by the addition of low-dose dopamine, enhanced renal and splanchnic but not cerebral blood flows during cardiopulmonary bypass.