Calculated Oxygen Delivery Research Articles

Cardiovascular effects of exercise induced dynamic hyperinflation in COPD patients-Dynamically hyperinflated and non-hyperinflated subgroups.

An increase in respiratory rate and expiratory flow limitation can facilitate dynamic hyperinflation (DH), which may cause an element of the intrathoracic pressure in connection with the worsening of venous return, with negative effect on stroke volume (SV) and cardiac output (CO). It has been unclassified, whether poor circulatory adaptation to exercise can be attributed to DH or poor cardio-vascular performance itself in COPD. Only a subset of COPD patients exhibit dynamic hyperinflation during exercise. We designed a study to show how lung mechanical and cardiovascular parameters change in hyperinflated and non-hyperinflated COPD patients during exercise with a new experimental set-up. Thirty-three COPD patients with similar severity of COPD and left ventricular performance (20 men, 13 women, mean±SD age: 65,36±6,95 years) participated. We measured the cardiovascular parameters with a non-invasive device (Finometer-pro) including the left ventricular ejection time index (LVETi) and estimated the change of DH with inspiratory capacity (IC) manoeuvres during exercise. Twenty-one subjects exhibited DH (DH group) and 12 did not (non-DH group). The measurement results were given in mean ± SD and difference between the values measured during maximal load and rest also (ΔX = Xmax.load-Xrest). ΔSV and ΔCO were significantly higher in non-DH vs. DH patients (ΔSV: non-DH 9,7 ± 13,22 ml vs. DH -3,6 ± 14,34 ml, p = 0.0142; ΔCO: non-DH 2,26 ± 1,46 l/min vs. DH 0,88 ± 1,35 l/min, p = 0.0024). LVETi was not different between the two groups. Calculated oxygen delivery (DO2) during maximal load was significantly higher in non-DH group. We concluded that worse cardiovascular adaptation to exercise of COPD patients can be associated with exercise-induced DH in a similar cardiovascular aged COPD group.

Identifying critical DO2 with compensatory reserve during simulated hemorrhage in humans.

Based on previous experiments in nonhuman primates, we hypothesized that DO2 crit in humans is 5-6ml O2 ·kg-1 min-1 . We measured the compensatory reserve (CRM) and calculated oxygen delivery (DO2 ) in 166 healthy, normotensive, nonsmoking subjects (97 males, 69 females) during progressive central hypovolemia induced by lower body negative pressure as a model of ongoing hemorrhage. Subjects were classified as having either high tolerance (HT; N=111) or low tolerance (LT; N=55) to central hypovolemia. HT and LT groups were matched for age, weight, BMI, and vital signs, DO2 and CRM at baseline. The CRM-DO2 relationship was best fitted to a logarithmic model in HT subjects (amalgamated R2 =0.971) and a second-order polynomial model in the LT group (amalgamated R2 =0.991). Average DO2 crit for the entire subject cohort was estimated at 5.3ml O2 ·kg-1 min-1 , but was ~14% lower in HT compared with LT subjects. The reduction in DO2 from 40% CRM to 20% CRM was 2-fold greater in the LT compared with the HT group. Average DO2 crit in humans is 5.3ml O2 ·kg-1 min-1 , but is ~14% lower in HT compared with LT subjects. The CRM-DO2 relationship is curvilinear in humans, and different when comparing HT and LT individuals. The threshold for an emergent monitoring signal should be recalibrated from 30% to 40% CRM given that the decline in DO2 from 40% CRM to 20% CRM for LT subjects is located on the steepest part of the CRM-DO2 relationship.

Abstract 11766: Late Gestation Fetal Oxygenation is Associated With Birthweight and Head Circumference in Patients With Cyanotic Congenital Heart Disease

Introduction: Abnormal fetal growth and development are evident in patients with cyanotic congenital heart disease (cCHD). However, the relationship between growth and fetal oxygenation is unknown. We sought to investigate the relationship between fetal hemodynamics and fetal growth in cCHD using fetal cardiovascular Magnetic Resonance Imaging (MRI). Hypothesis: The impaired fetal oxygenation would be associated with diminished fetal brain and body growth in cCHD. Methods: We performed a prospective observational study in fetuses diagnosed with cCHD at our institution from June 2010 to January 2020. Late-gestational fetal cardiovascular MRI was performed in 152 fetuses with cCHD to assess fetal blood flow (phase-contrast MRI) and oxygen saturation (T2 oximetry) in the major fetal vessels to calculate oxygen delivery to the brain and body according to our previously published techniques. Results are provided as medians with IQR and compared with 30 gestational age-matched normal controls using Mann-Whitney U test. A Pearson’s correlation was used to examine the relationships between variables. Results: Compared with normal controls, fetuses with cCHD had significantly reduced birth weight Z-scores [-0.41 (-0.29, 0.84) vs. -0.19 (-0.46, 0.37), p = 0.03], and neonatal head circumference Z-scores [0.1 (-1.75, 0.95) vs. 0.69 (0.1, 1.79), p = 0.003]. As a combined cohort, birthweight Z-score was correlated with fetal oxygen delivery (r = 0.33, p = 0.003), umbilical vein flow (r = 0.2, p = 0.006) and oxygen saturation (r = 0.25, p = 0.02). Birth head circumference Z-score was correlated with fetal cerebral oxygen delivery (r = 0.33, p = 0.01) and ascending aorta oxygen saturation (r = 0.33, p = 0.009). We also found an inverse relationship between ascending aorta oxygen saturation and superior vena cava flow (r = -0.24, p = 0.036). Conclusions: In conclusion, we observed associations between placental function in late gestation and birthweight, as well as cerebral oxygen delivery in utero and head circumference at birth. Our findings are in keeping with the concept that cCHD impacts fetal development through abnormal circulatory physiology and placental function.

An MRI approach to assess placental function in healthy humans and sheep.

Human placental function is evaluated using non-invasive Doppler ultrasound of umbilical and uterine artery pulsatility indices as measures of resistance in placental vascular beds, while measurement of placental oxygen consumption ( ) is only possible during Caesarean delivery. This study shows the feasibility of using magnetic resonance imaging (MRI) in utero to measure blood flow and oxygen content in uterine and umbilical vessels to calculate oxygen delivery to and by the gravid uterus, uteroplacenta and fetus. Normal late gestational human uteroplacental by MRI was ∼4mlmin-1 kg-1 fetal weight, which was similar to our MRI measurements in sheep and to those previously measured using invasive techniques. Our MRI approach can quantify uteroplacental , which involves the quantification of maternal- and fetal-placental blood flows, fetal oxygen delivery and , and the oxygen gradient between uterine- and umbilical-venous blood, providing a comprehensive assessment of placental function with clinical potential. It has not been feasible to perform routine clinical measurement of human placental oxygen consumption ( ) and in vitro studies do not reflect true metabolism in utero. Here we propose an MRI method to non-invasively quantify in utero placental and fetal oxygen delivery ( ) and in healthy humans and sheep. Women (n=20) and Merino sheep (n=10; 23sets of measurements) with singleton pregnancies underwent an MRI in late gestation (36±2weeks and 128±9days, respectively; mean±SD). Blood flow (phase-contrast) and oxygen content (T1 and T2 relaxometry) were measured in the major uterine- and umbilical-placental vessels, allowing calculation of uteroplacental and fetal and . Maternal (mlmin-1 kg-1 fetus) to the gravid uterus was similar in humans and sheep (human=54±15, sheep=53±21, P=0.854), while fetal (human=25±4, sheep=22 ± 5, P=0.049) was slightly lower in sheep. Uteroplacental and fetal (mlmin-1 kg-1 fetus; uteroplacental: human=4.1±1.5, sheep=3.5±1.9, P=0.281; fetus: human=6.8±1.3, sheep=7.2±1.7, P=0.426) were similar between species. Late gestational uteroplacental:fetal ratio did not change with age (human, P=0.256; sheep, P=0.121). Human umbilical blood flow (mlmin-1 kg-1 fetus) decreased with advancing age (P=0.008), while fetal was preserved through an increase in oxygen extraction (P=0.046). By contrast, sheep fetal was preserved through stable umbilical flow (mlmin-1 kg-1 ; P=0.443) and oxygen extraction (P=0.582). MRI derived measurements of uteroplacental and fetal between humans and sheep were similar and in keeping with prior data obtained using invasive techniques. Taken together, these data confirm the reliability of our approach, which offers a novel clinical 'placental function test'.

The impact of haemodilution and bypass pump flow on cerebral oxygen desaturation during cardiopulmonary bypass - A comparison of two systems of cardiopulmonary bypass

To determine the influence of haemodilution, bypass flow rates and calculated oxygen delivery during cardiopulmonary bypass (CPB) with either a conventional CPB (C-CPB) circuit or a miniaturised (Mini-CPB) circuit on cerebral oxygen desaturation. The effect of minimal haemodilution with a Mini-CPB was investigated. Eighty patients scheduled for elective cardiac surgery. Oxygenated haemoglobin (O2Hb) and tissue oxygenation index (TOI) were measured with near-infrared spectroscopy (NIRS). The average indexed bypass pump flow was significantly lower with Mini-CPB. When combined with haemoglobin concentration, the average oxygen delivery was the same between groups. Patients in the C-CPB group had a greater duration and severity of cerebral desaturation to a level <20% below baseline values, but none reached the depth and duration of the cerebral desaturation associated with poor outcome. Cerebral oxygen desaturation with C-CPB was significantly associated with low flows during bypass, whereas desaturation with Mini-CPB was associated with low perioperative haemoglobin concentration.

Assessment of global tissue perfusion and oxygenation in neonates and infants after open-heart surgery

Monitoring and preserving adequate perfusion and oxygen balance is a primary objective of critical care. This prospective observational study aimed to assess the relationship between global haemodynamic parameters and variables reflecting tissue oxygenation during the early period following corrective cardiac surgery in neonates and infants. The postoperative time course of oxygen delivery and consumption was evaluated. As surrogate markers of oxygen balance, the central venous oxygen saturation (ScvO2) and venoarterial PCO2 difference (PvaCO2) were thoroughly investigated. Thirteen children <1 year of age who underwent open-heart surgery were prospectively enrolled. In addition to conventional postoperative monitoring, transpulmonary thermodilution (TPTD) was used to monitor cardiac output and calculate oxygen delivery and consumption. In parallel with each TPTD measurement, arterial and central venous blood gas values were recorded. Global haemodynamic parameters and oxygenation measurements were compared with weighted linear regression statistics and Pearson's correlation coefficient. Data from 145 TPTD measurements and 304 blood gas samples were recorded. The early postoperative period was characterized by a supply-dependent oxygen consumption, as demonstrated by the direct correlation between the change in oxygen delivery and consumption (r = 0.62, P < 0.001). Regarding haemodynamic parameters, none of the heart rate, mean arterial pressure or cardiac index correlated with the measured ScvO2. However, the ScvO2 and PvaCO2 were found to correlate significantly (r = -0.49, P < 0.001), and both strongly related to oxygen extraction. Both the ScvO2 and PvaCO2 are reliable and comparable parameters in following tissue oxygen balance during the early postoperative course after open-heart surgery in neonates and infants. As part of multiparameter monitoring, our data highlight the importance of regular ScvO2 measurements and PvaCO2 calculations in paediatric intensive care.

The Risks of Blood Transfusion in Patients with Subarachnoid Hemorrhage

To the Editor: I read with much interest the recently published recommendations of the Neurocritical Care Society’s Consensus Conference on the ‘‘Critical Care management of patients following aneurysmal subarachnoid hemorrhage (SAH)’’ [1]. These guidelines state ‘‘there was wide agreement... that data supporting restrictive transfusion in medical patients do not apply to SAH’’ and that ‘‘patients should receive packed RBC transfusion to maintain hemoglobin concentration above 8–10 g/dl (moderate quality evidence, strong recommendation).’’ I believe that the literature does not support these recommendations. The pathophysiologic consequences following allogenic red blood cell (RBC) transfusion are complex and poorly understood [2]. It is however well recognized that RBC transfusions result in immunosuppression (perhaps lifelong) with an increased risk of infection (and tumor recurrence), are proinflammatory increasing the risk of acute lung injury and multi-organ failure as well as being prothrombotic [2–6]. The effects of RBC transfusion on tissue oxygenation are complex, with clinical and experimental data demonstrating that an increase in the calculated oxygen delivery does not necessarily translate into increased oxygen uptake, even in patients with an oxygen debt [7, 8]. Dhar et al. [9] evaluated the effect of RBC transfusion on oxygen kinetics in eight anemic patients following a SAH. While transfusion resulted in a 15% rise in hemoglobin and an 18% increase in calculated oxygen delivery, the global cerebral metabolic rate of oxygen (in ml/100 g/min) remained unchanged. In addition, it is important to recognize that the mean age of transfused blood in the United States in 24 days, being considerably older in major metropolitan medical centers [10]. ‘‘Aged’’ RBC’s have been shown to paradoxically decrease tissue oxygenation and are independent predictors of hospital complications and death in medical and surgical patients [7, 11–16]. Despite the fact that 13 million units of blood are transfused annually in the US and over 60 million worldwide [17], there is scanty evidence that non-bleeding, hemodynamically stable patients actually benefit from blood transfusion. Indeed, current data suggest that in these patients blood transfusion increases the risk of infection, ARDS, and death [18]. Anemia is a common finding in patients who have suffered a SAH, with over 50% of patients having a nadir hematocrit less than 30% [19–22]. Multiple factors likely contribute to the development of an anemia following SAH, including blood loss during surgery, venesection, gastrointestinal and other sources of blood loss, decreased production of erythropoietin, and impaired erythropoiesis [22]. The nadir hemoglobin is generally related to the admission Hunt and Hess grade [21, 22]. Anemia after SAH has been reported to be associated with worse outcomes [21, 23]. The association between anemia and worse outcomes does not necessarily imply that correction of the anemia with blood transfusions will improve outcome. This is important, as data suggest that between 35 and 60% of patients suffering a SAH receive a blood transfusion during their hospitalization [21–26]. Apart from the risks noted in ICU patients, there may be additional risks of blood transfusion in patients with SAH. Nitric oxide (NO) plays a critical role in regulating vasomotor tone and NO metabolism may influence the risk and severity of vasospasm after SAH [27]. Erythrocytes carry NO for release in vessels, whereas transfused erythrocytes lack stored NO and may exacerbate vasospasm [28, 29]. P. E. Marik (&) Department of Medicine, Eastern Virginia Medical School, 825 Fairfax Ave, Suite 410, Norfolk, VA 23507, USA e-mail: marikpe@evms.edu

Effects of Anemia and Hypotension on Porcine Optic Nerve Blood Flow and Oxygen Delivery

Perioperative ischemic optic neuropathy occurs after major surgical procedures, which are often associated with hypotension, anemia, or venous congestion. However, the effects of these conditions on optic nerve (ON) blood flow are unknown and cannot be studied adequately in humans. Farm-raised pigs were anesthetized with isoflurane, kept normocapnic and normothermic, and subjected to conditions of euvolemic or hypovolemic hypotension (mean arterial pressure 50-55 mm Hg), anemia (hematocrit 17%), venous congestion, and combinations thereof. Control animals were kept euvolemic and normotensive for the entire experiment. Fluorescent microspheres were used to measure cerebral blood flow (CBF) and ON blood flow at baseline and after experimental conditions, and to calculate oxygen delivery (DO2). No significant changes in CBF or ON blood flow or DO2 occurred with euvolemic hypotension (n = 5), compared with controls (n = 12). Hypovolemic hypotension (n = 4) resulted in stable CBF and cerebral DO2, but significant reductions in ON DO2 (P = 0.032). The significant increase in CBF associated with anemia (n = 6) resulted in stable cerebral DO2. In contrast, ON blood flow did not significantly change with anemia, with (n = 5) or without (n = 6) euvolemic hypotension, resulting in significant reductions in ON DO2 (P < 0.01). Compensatory mechanisms for porcine CBF maintain stable DO2 under specified conditions of hypotension or anemia, whereas ON compensatory mechanisms were unable to maintain blood flow and to preserve DO2. The authors conclude that the porcine ON is more susceptible to physiologic perturbations than the brain.

The Correlation of Near-Infrared Spectroscopy with Changes in Oxygen Delivery in a Controlled Model of Altered Perfusion

Alterations in regional tissue perfusion may precede global indications of shock. This study compared regional tissue oxygenation saturation (StO2) using near-infrared spectroscopy with standard hemodynamic and biochemical variables in 40 patients undergoing cardiopulmonary bypass (CPB). Mean arterial pressure, cardiac output, oxygen delivery, arterial blood gases, and lactate were recorded at specific intervals during surgery. Data were organized by stage of procedure, and the relationship of StO2 to established parameters was investigated. With initiation of CPB, StO2 declined by 12.9 per cent (standard deviation +/- 14.75%) with a delayed increase in lactate from 0.9 (interquartile range [IQR], 0.6-1.5) mmol/L to 2.3 (IQR, 1.8-2.5) mmol/L. The minimum StO2 value preceded the maximum lactate level by an average time of 93.9 (standard deviation +/- 86.3) minutes. Additionally, a decrease in StO2 corresponded with an increase in base deficit of 4.84 (standard deviation +/- 2.37) mEq/L over the same period. Calculated oxygen delivery decreased from a baseline value of 754 (IQR, 560-950) mL/min to 472 (IQR, 396-600) mL/min with initiation and maintenance of CPB. For patients undergoing CPB, StO2 is a reliable, noninvasive monitor of perfusion, which correlates well with oxygen delivery and identifies perfusion deficits earlier than lactate or base deficit.

The impact of an hematocrit of 20% during normothermic cardiopulmonary bypass for elective low risk coronary artery bypass graft surgery on oxygen delivery and clinical outcome – a randomized controlled study [ISRCTN35655335

IntroductionCardiopulmonary bypass (CPB) induces hemodilutional anemia, which frequently requires the transfusion of blood products. The objective of this study was to evaluate oxygen delivery and consumption and clinical outcome in low risk patients who were allocated to an hematocrit (Hct) of 20% versus 25% during normothermic CPB for elective coronary artery bypass graft (CABG) surgery.MethodsThis study was a prospective, randomized and controlled trial. Patients were subjected to normothermic CPB (35 to 36°C) and were observed until discharge from the intensive care unit (ICU). Outcome measures were calculated whole body oxygen delivery, oxygen consumption and clinical outcome. A nonparametric multivariate analysis of variance for repeated measurements and small sample sizes was performed.ResultsIn a total of 54 patients (25% Hct, n = 28; 20% Hct, n = 26), calculated oxygen delivery (p = 0.11), oxygen consumption (p = 0.06) and blood lactate (p = 0.60) were not significantly different between groups. Clinical outcomes were not different between groups.ConclusionThese data indicate that an Hct of 20% during normothermic CPB maintained calculated whole body oxygen delivery above a critical level after elective CABG surgery in low risk patients. The question of whether a transfusion trigger in excess of 20% Hct during normothermic CPB is still supported requires a larger prospective and randomized trial.

Myocardial perfusion reserve in adults with cyanotic congenital heart disease

In patients with cyanotic congenital heart disease (CCHD), a right-to-left shunt results in systemic hypoxemia. Systemic hypoxemia incites a compensatory erythrocytosis, which increases whole blood viscosity. We considered that these changes might adversely influence myocardial perfusion in CCHD patients. Basal and hyperemic (intravenous dipyridamole) perfusion measurements were obtained with [13N]ammonia positron emission tomographic imaging in left (LV) and right (RV) ventricular and septal myocardium in 14 adults with CCHD [age: 34.1 yr (SD 6.5)]; hematocrit: 62.2% (SD 4.8)] and 10 healthy controls [age: 34.1 yr (SD 6.5)]. In patients, basal perfusion measurements were higher in LV [0.77 (SD 0.24) vs. 0.55 ml x min(-1) x g(-1) (SD 0.09), P < 0.02], septum [0.71 (SD 0.16) vs. 0.49 ml x min(-1) x g(-1) (SD 0.09), P < 0.001], and RV [0.77 (SD 0.30) vs. 0.38 ml x min(-1) x g(-1) (SD 0.09), P < 0.001]. However, basal measurements normalized for the rate-pressure product were similar to those of controls. Calculated oxygen delivery relative to rate-pressure product was higher in the patients [2.2 (SD 0.8) vs. 1.6 (SD 0.4) x 10(-5) ml O2 x min(-1) x g tissue(-1) x (beats x mmHg)(-1) in the LV, P < 0.05, and 2.0 (SD 0.7) vs. 1.4 (SD 0.3) x 10(-5) ml O2 x min(-1) x g tissue(-1) x (beats x mmHg)(-1) in the septum, P < 0.01]. Hyperemic perfusion measurements in CCHD patients did not differ from controls [LV, 1.67 (SD 0.60) vs. 1.95 ml x min(-1) x g(-1) (SD 0.46); septum, 1.44 (SD 0.56) vs. 1.98 ml x min(-1) x g(-1) (SD 0.69); RV, 1.56 (SD 0.56) vs. 1.65 ml x min(-1) x g(-1) (SD 0.64), P = not significant], and coronary vascular resistances were comparable [LV, 55 (SD 25) vs. 48 mmHg x ml(-1) x g x min (SD 16); septum, 67 (SD 35) vs. 50 mmHg x ml(-1) x g x min (SD 21); RV, 59 (SD 26) vs. 61 mmHg x ml(-1) x g x min (SD 27), P = not significant]. These findings suggest that adult CCHD patients have remodeling of the coronary circulation to compensate for the rheologic changes attending chronic hypoxemia.

Specific angiotensin II receptor blockage improves intestinal perfusion during graded hypovolemia in pigs.

To investigate the potential of specific angiotensin II subtype 1 (AT1) receptor blockade to modify the mesenteric hemodynamic response to acute hypovolemia and retransfusion. Prospective, randomized, controlled experimental study. University-affiliated animal research laboratory. Fasted, anesthetized, ventilated, juvenile domestic pigs of both sexes. Acute, graded hypovolemia by 20% and 40% of the total estimated blood volume followed by retransfusion in control animals (CTRL; n = 10) and animals pretreated with the AT1 receptor blocker candesartan (CAND; n = 10). Invasive monitoring of arterial and central venous blood pressures, cardiac output, portal venous blood flow, and jejunal mucosal blood flow. Blood gases were repeatedly analyzed to calculate oxygen delivery and consumption. Thirty minutes after each level of hypovolemia at 20% and 40%, cardiac output was decreased in CTRL animals from a baseline of 2.9 +/- 0.1 to 1.8 +/- 0.2 and 1.1 +/- 0.2 L/min, with no differences compared with CAND animals. Cardiac output was restored to 3.0 +/- 0.3 L/min 30 mins after retransfusion in CTRL animals, with no significant intergroup differences. Baseline portal venous blood flow (Q(MES)) and jejunal mucosal perfusion (PU(JEJ)) were greater in CAND animals compared with CTRL animals. During graded hypovolemia, CAND animals maintained Q(MES) and PU(JEJ) at significantly higher levels compared with CTRL animals, particularly after 40% hemorrhage (+221% and + 244%, respectively, relative to the mean values in CTRL animals). The same pattern was observed after retransfusion. Moreover, the calculated mesenteric critical oxygen delivery was significantly greater in CTRL animals (74 mL/min) compared with CAND animals (34 mL/min). No animals died in the CAND group, whereas four animals died during 40% hypovolemia or retransfusion in the CTRL group. Specific AT1 blockade before acute hypovolemia significantly ameliorated mesenteric and, in particular, jejunal mucosal hypoperfusion. In addition, cardiovascular stability was improved, and mortality in conjunction with acute hypovolemia and retransfusion could be completely avoided. These findings support a fundamental role of the renin-angiotensin system in the mesenteric response to acute hypovolemia and indicate a substantial interventional potential for candesartan in conjunction with circulatory stress.

Haemodynamic effects of diaspirin crosslinked haemoglobin (DCLHb) given before abdominal aortic aneurysm surgery

We studied 34 patients undergoing elective repair of an abdominal aortic aneurysm under combined general anaesthesia and epidural block to evaluate the acute effects of diaspirin crosslinked haemoglobin (DCLHb) 50, 100 and 200 mg kg-1 i.v. Haemodynamic variables were measured continuously using pulmonary and radial artery catheters, and oxygen delivery and consumption were calculated at regular intervals. DCLHb was shown to be vasoactive, producing an increase in mean arterial pressure of approximately 25% with each dose, with small decreases in cardiac index and calculated oxygen delivery. These effects persisted beyond the end of infusion and provided a degree of cardiovascular stability during the operative procedure. The effects of DCLHb on oxygen consumption at these doses were minimal.

Clinical assessment and measurement of oxygen transport in the critical care setting

Adequate delivery of oxygen to the tissues is an important factor both in the initial resuscitation of the shocked patient and subsequently in the development of multiple organ failure. The advent of the pulmonary artery catheter has facilitated the calculation of global measurements of oxygen transport at the bedside. Calculated oxygen delivery in fact represents arterial oxygen dispatch rather than actual oxygen delivery to the respiring tissues. Considerable controversy still surrounds the issue of resuscitation of critically ill patients to predetermined goals for oxygen delivery and consumption. More recently interest has arisen in other measures of oxygen transport, in particular regional techniques such as the gastric tonometer.

Evaluation of the Capabilities of a Hemoglobin Vesicle as an Artificial Oxygen Carrier in a Rat Exchange Transfusion Model

Encapsulation of hemoglobin within a liposome is one of the strategies in the development of artificial oxygen carriers. It maintains the oxygen transporting properties of hemoglobin and, at the same time, eliminates the side effects of cell free hemoglobin. Hemoglobin vesicles (HbV) are a type of liposome encapsulated hemoglobin. They have a particle size of approximately 250 nm, a hemoglobin concentration of 10 g/dl, and the oxygen affinity, P50, is regulated to 32 Torr. In this study the authors examined the oxygen transporting capability of HbV in vivo, by performing exchange transfusions in rats. Exchange transfusion (90% of the estimated circulatory volume) with HbV suspended in 5% albumin (containing 160 mEq/L, sodium and 107 mEq/L, chloride) was carried out in male Wistar rats. Mean arterial pressure and heart rate were monitored through the arterial catheter. Arterial blood samples for gas analyses were also obtained from the arterial catheter. Abdominal aortic blood flow was measured by an ultrasonic pulsed Doppler flowmeter as an indicator of cardiac output. The oxygen tension of blood withdrawn from the right atrium was measured as an indicator of mixed venous oxygen tension. These values were employed to calculate oxygen delivery and consumption. Renal cortical and skeletal muscle tissue oxygen tensions were monitored as indicators of tissue perfusion. Five percent albumin and washed rat red blood cells suspended in 5% albumin containing 10 g/dl of hemoglobin; were employed as controls. At the completion of a 90% exchange transfusion, renal cortical and skeletal muscle tissue oxygen tensions, along with oxygen delivery and consumption, were sustained almost equally well with the HbV suspension compared to the washed rat red blood cell suspension, but declined significantly with the albumin suspension. The results indicate that the oxygen transporting capability of HbV was almost equivalent to that of rat red blood cells.

The use of esmolol in whole-body hyperthermia: Cardiovascular effects

Whole-body hyperthermia (WBH) is a well-described investigational adjunct to systemic chemotherapy for the treatment of advanced malignancies. The hemodynamic consequences of this physiologic state may include tachycardia, which can produce acute myocardial ischemia in patients with coronary artery disease. Ischemic heart disease is currently considered a contraindication to WBH. We chose to investigate the consequences of using a new β1-adrenergic antagonist, esmolol, to attempt to control the tachycardia associated with WBH. After institutional approval and patient consent, nine consecutive patients with normal cardiac function presenting for WBH with carboplatin infusion were studied. Along with standard monitors, radial arterial and oximetric thermodilution pulmonary artery catheters were placed. Patients were sedated and heated in a radiant warmer (Enthermics). Spontaneous ventilation was maintained and hemodynamic data were gathered at 37°C, and at 41.8°C (before, during and after esmolol infusion). Heart rate and cardiac output increased (by 46% (p = 0.001) and 35% (p=0.04) respectively) while mean arterial pressure and systemic vascular resistance fell (by 18% (p = 0.02) and 44% (p = 0.006) respectively) during hyperthermia. Heart rate was significantly reduced during esmolol administration (mean dose 180 μg/kg/min) in the absence of changes in cardiac index and calculated oxygen delivery. Ventricular filling pressures and stroke work were unchanged. No heart failure, pulmonary edema, or other adverse event was observed. Hemodynamic changes seen during esmolol administration were completely reversed 15 min after the infusion was stopped. We conclude that the administration of moderate doses of esmolol is safe for this population of patients undergoing WBH, and that this technique raises the question of whether patients with ischemic heart disease could safely undergo WBH.

Improved Haemodynamic Stability with Administration of Aprotinin During Orthotopic Liver Transplantation

In a placebo-controlled, double-blind study, we have investigated the hypothesis that patients for orthotopic liver transplantation (OLT) treated with high-dose aprotinin (serum concentrations > or = 200 kiu ml-1) show greater haemodynamic stability on graft reperfusion. We studied 55 adult patients presenting for OLT, and 52 were included in the analysis. The treatment and placebo groups were similar in patient characteristics. The anaesthetic regimen used was standardized, and veno-venous bypass were used in all patients. Cardiac output measurements and haemodynamic profiles were recorded at intervals throughout anaesthesia and surgery. Arterial and mixed venous oxygen saturations were measured by co-oximetry. Derived variables were measured using standard formulae. Aprotinin treated patients had greater values for systemic vascular resistance on reperfusion, with a lesser cardiac index and calculated oxygen delivery. Oxygen consumption, however, was significantly greater, despite reduced delivery.

Intermittent hemodialysis in critically ill patients with multiple organ dysfunction syndrome is associated with intestinal intramucosal acidosis.

Conventional intermittent hemodialysis in the critically ill patient can be associated with hemodynamic and respiratory instability. Intermittent hemodialysis induced arterial hypotension might be detrimental. We therefore studied the influence of intermittent hemodialysis on systemic and regional oxygen transport in critically ill patients. Prospective descriptive study. Medical/surgical 24-bed intensive care unit in a university hospital. Eleven critically ill patients admitted to the intensive care unit (APACHE III score: 82 +/- 12) and developing multiple organ dysfunction syndrome with acute renal failure. All patients were mechanically ventilated and hemodynamically stable with inotropic support. Systemic oxygen transport variables were calculated, and arterial blood lactate concentration was measured before, during, and after intermittent hemodialysis. Tonometer PCO2 was measured using a tonometer, and arterial-tonometer CO2 gap was used as an indicator of intestinal intramucosal acidosis. Intermittent hemodialysis induced an increase in calculated systemic oxygen consumption (P < 0.01). During intermittent hemodialysis there was a significantly higher need of inotropic support (P < 0.05) to maintain arterial blood pressure, cardiac index, and calculated systemic arterial oxygen delivery. The arterial-tonometer CO2 gap increased significantly during and after the procedure. In critically ill patients with multiple organ dysfunction syndrome intermittent hemodialysis induces an increase in oxygen consumption. Despite higher inotropic support to maintain systemic calculated oxygen delivery intestinal intramucosal acidosis occurs during intermittent hemodialysis and may even persist after the procedure is terminated.

Influence of severe hemodilution on brain function and brain oxidative metabolism in the cat.

It has been established that during constant pressure arterio-venous bypass perfusion, brain metabolism gradually deteriorates in parallel with the declining hematocrit. However, whether this is due to a disturbance of flow regulation or to the decline in the oxygen-carrying capacity of the blood has not been documented. Therefore, intact animals were submitted to severe hemodilution to determine the threshold for the beginning of functional and biochemical impairment of the brain. Six anesthetized and paralyzed adult mongrel cats were submitted to gradual isovolemic hemodilution by stepwise exchange of blood with Ringer lactate/dextran (1 : 1) solution. Exchange of 80 ml/kg body weight resulted in a final hematocrit level ranging from 6.1% to 11%. Cerebral blood flow gradually increased during hemodilution, with a sharp rise to eight times the prehemodilution value when the hematocrit fell below 10%. The calculated oxygen delivery to the brain remained relatively unchanged. Hemodilution did not cause suppression of spontaneous ECoG or somatically evoked primary cortical potentials, even at the lowest hematocrit value of 6.1%. Brain tissue ATP and phosphocreatine content were largely maintained, although tissue lactate content was elevated (9.54 +/- 5.99 micromol/g). The hemodynamically unimpaired healthy mammal is able to support a substantial degree of hemodilution without major functional or biochemical disturbance to the brain. The previously observed disturbances during prolonged bypass perfusion are, therefore, most probably due to the associated abnormalities of flow regulation.

Improved haemodynamic stability with administration of aprotinin during orthotopic liver transplantation

In a placebo-controlled, double-blind study, we have investigated the hypothesis that patients for orthotopic liver transplantation (OLT) treated with high-dose aprotinin (serum concentrations > or = 200 kiu ml-1) show greater haemodynamic stability on graft reperfusion. We studied 55 adult patients presenting for OLT, and 52 were included in the analysis. The treatment and placebo groups were similar in patient characteristics. The anaesthetic regimen used was standardized, and veno-venous bypass were used in all patients. Cardiac output measurements and haemodynamic profiles were recorded at intervals throughout anaesthesia and surgery. Arterial and mixed venous oxygen saturations were measured by co-oximetry. Derived variables were measured using standard formulae. Aprotinin treated patients had greater values for systemic vascular resistance on reperfusion, with a lesser cardiac index and calculated oxygen delivery. Oxygen consumption, however, was significantly greater, despite reduced delivery.