Penny S. Reynolds

Assessing shock resuscitation strategies by oxygen debt repayment.

Identification of occult shock is a major clinical problem compounded by inadequate criteria for assessing the efficacy of fluid resuscitation. We suggest that these problems may be resolved in part by understanding both the physiological mechanisms underlying oxygen debt accumulation and, more importantly, the debt repayment schedule during resuscitation. We present a simplified tutorial that incorporates the concept of the oxygen supply-delivery relationship with that of oxygen debt and show how this is relevant to the understanding of shock and resuscitation. Use of oxygen debt metrics as end points for shock have been controversial; however, much of the controversy may have been due to incomplete understanding of basic physiology of shock and semantic confusion between the various metrics proposed as end points. Here, we provide working definitions for the frequently misunderstood concepts of oxygen deficit and oxygen debt and discuss the relatively novel concept of oxygen debt repayment schedule. We introduce predictions made on the basis of data derived from animal models of hemorrhagic shock. Our calculations suggest that the amount of debt repaid in the first 2 h of resuscitation, rather than the restoration of volume per se, influences the likelihood of organ damage. Because of difficulties inherent in measuring oxygen debt in the prehospital and emergency settings, various metabolic end points such as lactate and base deficit have been proposed as surrogates. We demonstrate the heuristic value of this model in providing a predictive framework for both the optimum therapeutic time window and optimum fluid loadings before critical transitions to an irreversible shock state can occur. The model also provides an unambiguous and objective standard for quantifying the behavior of various postulated shock markers.

Resonance Raman spectroscopy: a new technology for tissue oxygenation monitoring.

Objective:To evaluate resonance Raman spectroscopy for the detection of changes in sublingual mucosal hemoglobin oxygen saturation (Smo2) in response to hemorrhage and resuscitation, and to compare Smo2 with other indicators of tissue oxygenation including central venous oxygen saturation (Scvo2), lactate, base excess, and shed blood volume. Design:Prospective single group pilot study. Setting:University laboratory. Subjects:Five Sprague-Dawley rats. Interventions:Animals were anesthetized and instrumented for measurement of arterial and central venous blood gases. Raman spectroscopy was performed using a krypton ion laser providing excitation at 406.7 nm (5 mW). A 1-mm2 region of the sublingual tongue surface was chosen for investigation. Animals were subjected to stepwise hemorrhage until approximately 50% of the blood volume was removed. At each hemorrhage and resuscitation interval, Raman spectroscopy was performed and corresponding arterial and central venous blood gas and lactate measurements were made. Smo2 was calculated as the ratio of the oxygenated heme spectral peak height to the sum of the oxy- and deoxyhemoglobin spectral peak heights. Raman spectroscopy-derived Smo2 measurements were compared with Scvo2 as well as with other indicators of oxygenation. Measurements and Main Results:The mean difference between Smo2 and Scvo2 for all paired measurements was 5.8 ± 11.7 absolute saturation points. Smo2 was significantly (p < .0001) correlated with Scvo2 (r = .80), lactate (r = −.78), base excess (r = .80), and shed blood volume (r = −.75). Smo2 and Scvo2 showed similar levels of precision for predicting elevated lactate and base deficit. Conclusions:These studies demonstrate the ability of Raman spectroscopy to noninvasively track microvascular hemoglobin oxygenation in tissue and favorably correlate with other important indicators of tissue oxygenation such as Scvo2, lactate, base deficit, and shed blood volume. The technique shows promise as a method to noninvasively monitor tissue oxygenation.

Lactate profiles as a resuscitation assessment tool in a rat model of battlefield hemorrhage resuscitation.

Time profiles of arterial lactate concentrations have been proposed as markers for both the degree of physiological derangement during shock and effectiveness of clinical resuscitation, but have not been evaluated for use in short-term experimental protocols. We developed two quantitative mixed models of sequential arterial lactate concentrations to evaluate competing low-volume (<4 mL/kg) battlefield resuscitation therapies in a rat model of acute severe hemorrhagic shock: a simple linear additive model and a nonlinear mechanistic model that described lactate profiles in a continuous trajectory with a defined turning point. Data were obtained during a study evaluating a novel hemoglobin polymer (OxyVita) in a cocktail of hypertonic saline and Hextend as an alternative to standard Hextend. Fluids were either infused by titration to a mean systolic pressure of 60 mmHg or as a single bolus. Parameter estimates derived from both models were assessed for evidence of treatment efficacy and as indicators of short-term survival. A cocktail of hypertonic saline and Hextend was superior to standard Hextend in enhancing survival; however, lactate profiles did not differ between treatments. Regardless of resuscitation regimen, animals surviving to at least 60 min posthemorrhage can be discriminated from nonsurvivors by significantly lower peak lactates (a difference of at least 3 mM; P < 0.001), and all survivors exhibited a decline in lactate with resuscitation. Sequential measurements of lactate over relatively short time frames during resuscitation are of value in assessing both response to resuscitation and short-term mortality.

Effects of a combination hemoglobin based oxygen carrier–hypertonic saline solution on oxygen transport in the treatment of traumatic shock

BACKGROUNDnLogistics complicate fluid resuscitation of traumatic shock on the battlefield. Traumatic shock can result in oxygen debt (O(2)D) accumulation that is fatal. However, the ability of fluid strategies to repay O(2)D are not commonly reported. This pilot study examined various resuscitation fluids, including a combination of PEGylated bovine hemoglobin and hypertonic saline (AfterShock™) on their ability to repay O(2)D in traumatic shock.nnnMETHODSn41 anesthetized swine underwent hemorrhage to an O(2)D of 80 mL/kg. Animals received one of the following: 500 mL whole blood, 500 mL AfterShock™, 500 mL hypertonic (7.2%) saline, 250 mL hypertonic (7.2%) saline, 500 mL Hetastarch (6%), or 500 mL lactated Ringers. Oxygen transport variables (O(2)D, oxygen consumption, oxygen delivery, central venous hemoglobin oxygen saturation, oxygen extraction ratios), lactate clearance, and survival were monitored for 3h after treatment. Data were analyzed using mixed-model ANOVA and comparisons were made to the performance of whole blood.nnnRESULTSnOnly animals receiving AfterShock™, 500 mL hypertonic saline, and 500 mL Hetastarch survived to 180 min. While not statistically significant AfterShock™ demonstrated trends in improving the repayment of O(2)D and in improving oxygen transport variables despite having lower levels of global oxygen delivery compared to whole blood, Hetastarch and 500 mL hypertonic saline groups.nnnCONCLUSIONnUse of 500 mL AfterShock™, 500 mL of 7.2% saline or 500 mL of Hetastarch resulted in improved short-term survival. While not statistically significant, AfterShock™ demonstrated trends in improving O(2)D. These findings may have implications for designing resuscitation fluids for combat casualty care.

A novel noninvasive impedance-based technique for central venous pressure measurement

Knowledge of central venous pressure (CVP) is considered valuable in the assessment and treatment of various states of critical illness and injury. We tested a noninvasive means of determining CVP (NICVP) by monitoring upper arm blood flow changes in response to externally applied circumferential pressure to the upper arm veins. Thirty-six patients who were undergoing CVP monitoring as part of their care had NICVP determined and compared with CVP. Volume changes were measured in the upper arm using tetra-polar impedance plethysmography underneath a blood pressure cuff. The cuff was inflated over 5 s to a pressure greater than CVP but less than diastolic arterial pressure. After 45 to 60 s, the cuff was rapidly deflated. Noninvasive CVP was determined as the cuff pressure noted at the maximum derivative of the volume increase under the cuff during deflation. Noninvasive CVP was then compared with invasively measured CVP taken during the same period by Bland-Altman analysis. A total of 108 trials (three per subject) were performed on 36 patients. Mean bias was −0.26 mmHg (95% confidence interval [CI]: −0.67, 0.15). Limits of agreement were −2.7 and 2.2 mmHg with the 95% CI for the lower limit of agreement (−3.4, −2.0 mmHg) and for the upper limit of agreement (1.5, 2.9 mmHg). Correlation between CVP and NICVP was 0.95 (95% CI: 0.93 to 0.97; P < 0.0001). Noninvasive CVP as determined in this study may be a clinically useful substitute for traditional CVP measurement and may offer a tool for early diagnosis and treatment of acute states in which knowledge of CVP would be helpful.

The first documented cardiac arrest rhythm in hospitalized patients with heart failure.

BACKGROUNDnPatients with heart failure (HF) have abnormal cellular anatomy and myocardial mechanics that may impact the initial rhythm and subsequent outcomes in cardiac arrest (CA).nnnHYPOTHESISnPatients with pre-existing HF are less likely to have ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT) as the first documented rhythm in CA and have poorer survival than patients without pre-existing HF.nnnPURPOSEnIdentify the first documented cardiac arrest rhythm (FDR) in hospitalized patients with and without a pre-existing history of HF.nnnMETHODSnWe evaluated 60,389 consecutive, adult, index, pulseless CA events with documented initial rhythm in the National Registry of Cardiopulmonary Resuscitation. The primary endpoint was the FDR in patients with and without a history of pre-existing HF. Secondary endpoints were return of spontaneous circulation (ROSC), survival to discharge, and neurological outcome.nnnRESULTSnThirty three percent of patients had a pre-existing diagnosis of HF. HF patients were more likely to have VF/pVT (25.9 vs. 23.2%) and less likely to have asystole (34.4 vs. 35.3%, p=<.0001) than non-HF. There was no difference in survival to discharge (18.3 vs. 18.2%, p=.66), or good neurological outcomes (82.2 vs. 83.2%, p=.23) between the groups. Women were less likely to have VF/pVT as the first documented rhythm in both HF and non-HF groups.nnnCONCLUSIONSnHospitalized patients with HF are more likely than those without HF to have VF/pVT as the FDR in CA, however the clinical magnitude of this difference is small. Overall survival and neurological outcomes are no different than hospitalized arrest patients without HF.