Prior to any human procedure, the institutional review board (IRB) must approve the protocol. The protocol used in this study was approved by the US Army Medical Research and Materiel Command IRB. The protocol is designed to demonstrate the physiological responses of compensation to a progressive reduction in central blood volume similar to that experienced by individuals during ongoing hemorrhage in a controlled and reproducible laboratory setting. The laboratory room temperature is controlled at 23 – 25 ˚C.
1. Equipment Preparation
2. Subject Preparation
3. Performing the LBNP Protocol
The LBNP procedure causes a reduction in air pressure around the lower torso and legs. As this vacuum is progressively increased, blood volume shifts from the head and upper torso to the lower body to create a state of central hypovolemia. The progressive reduction in central blood volume (i.e., LBNP) produces significant alterations in the features of the arterial waveform measured with the infrared finger photoplethysmograph (Figure 5). The Compensatory Reserve Index (CRI) is calculated from the recorded arterial pulse wave using a unique machine learning algorithm which analyzes changes in wave form characteristics to calculate an estimated compensatory reserve (Figure 6).1,15,16 Each continuous noninvasive photoplethysmograph waveform (represented as the monitored 'Patient's Arterial Waveform') is the input to calculate an estimate of an individual's compensatory reserve (represented as the 'CRI Estimate') based on comparison to a large 'library' of reference waveforms (represented as the 'Algorithm Waveform Library') generated from progressive levels of central hypovolemia.
In this experiment, a subject was exposed to LBNP until the onset of hemodynamic decompensation which occurs when the body is no longer able to compensate for the hypovolemia. The values for mean arterial pressure, heart rate, SpO2, and CRI plotted against time (i.e., progressive reductions in central blood volume caused by increasing levels of LBNP) are shown in Figure 7. The results of the experiment show that changes in mean arterial pressure, heart rate, and SpO2 occur during the later phases of hemorrhage (i.e., >15 min into the protocol for heart rate and >25 min for mean arterial pressure and SpO2) while CRI decreases early and progressively throughout the multiple steps of LBNP.
Tolerance to reduced central blood volume is defined as the time from the start of the experiment to decompensation. In this example, tolerance was approximately 27.5 min at a level of -70 mmHg LBNP. Based on previous experiments that were designed to equate the magnitude of actual blood loss with LBNP,8 the equivalent blood loss that our subject was able to tolerate was estimated at approximately 1.2 L.
Figure 1: LBNP Chamber. A subject is shown in a supine position on the bed of the LBNP chamber. The neoprene skirt around the subject's waist is used to create an airtight seal within the LBNP chamber. Previously published in Cooke et al.17 Please click here to view a larger version of this figure.
Figure 2: Compensatory Reserve Monitoring Device. The device consists of a noninvasive finger pulse oximeter that transmits pulse oximeter and waveform data via a USB connection to a compensatory reserve monitor. The monitor unit contains an algorithm which calculates a value for compensatory reserve known as the Compensatory Reserve Index (CRI)1,12. Data are recorded at each heart beat and displayed on the monitor and stored on a memory card. Please click here to view a larger version of this figure.
Figure 3. Stepwise Changes in LBNP During Experiment. During the experimental protocol, LBNP (mmHg) is adjusted in a stepwise manner (5 min/level) to induce progressive central hypovolemia. This diagram shows LBNP increasing from 0 to -100 mmHg during 40 min of an experimental protocol. Modified from Convertino et al.18 Please click here to view a larger version of this figure.
Figure 4: Hemodynamic Decompensation. Sample blood pressure (mm Hg, yellow tracing) and lower body negative pressure (mmHg, white tracing) recordings are shown from a subject at the point of hemodynamic decompensation. At the point of decompensation, blood pressure is 78/55 mmHg, and lower body negative pressure is -60 mmHg. Blood pressure returns to normal after cessation of lower body negative pressure. Modified from Convertino et al.1 Please click here to view a larger version of this figure.
Figure 5. Arterial Waveforms During LBNP. Sample recordings of arterial pressure waveforms are shown during baseline (upper tracing) and during -60 mmHg lower body negative pressure (LBNP, lower tracing). The changes in the characteristic features of the arterial waveforms are evaluated to estimate compensatory reserve. Please click here to view a larger version of this figure.
Figure 6: How the CRI is Calculated. Diagram illustrating the process of the compensatory reserve index (CRI) algorithm that compares beat-to-beat arterial blood pressure waveform tracings over an interval of 30 heartbeats (A) to a 'library' of waveforms (B) collected from humans exposed to progressive reductions in central blood volume for generation of an estimated CRI value (C). Reproduced from Convertino et al.15 Please click here to view a larger version of this figure.
Figure 7. Sample Results of an LBNP Experiment. Values of Mean Arterial Pressure (MAP, mmHg), Heart Rate (HR, beats/min), arterial oxygen saturation (SpO2, %), Compensatory Reserve Index (CRI) and Lower Body Negative Pressure (LBNP, mmHg) are shown for one subject during an LBNP experiment. The dashed line represents the onset of cardiovascular decompensation, Please click here to view a larger version of this figure.
Figure 8: Characteristic Features of the Arterial Waveform. Two wave forms are shown that demonstrate the characteristic features of the arterial ejected and reflected waveforms during normovolemia and hypovolemia. The red line indicates the integrated waveform that is recorded and observed in a tracing. Previously published in Convertino et al.1 Please click here to view a larger version of this figure.
Dynamic Research Evaluation Workstation (DREW) data acquisition syetem | NA | NA | Custom Built by ISR personnel. The DREW allows for time synchronization of both digital and analog signal data collection from up to 16 independent instruments with a sampling rate of 1000 Hz. |
Finometer | Finapress Medical Systems (FMS) | Model 1 | Device that provides non-invasive, continuous measurements of brachial artery blood pressure and arterial oxygen saturation (SpO2) using two separate infrared finger photophlethymography cuff sensors. |
BCI Capnocheck Plus | Smith Medical PM Inc. | 9004 | Capnograph used to measure end tidal CO2 and respiration rate |
CipherOX | Flashback Technologies Inc. | R200 | Investigational device used to calculate Compensatory Reserve Index (CRI) |
Nonin 9560 Pulse Oximeter | Nonin | 9560 | finger pulse oximeter |
Lower Body Negative Pressure Chamber (LBNP) | NASA | 79K32632-1 | Custom Chamber built by NASA |
ECG Biotach | Gould | 13-6615-65 | Electrocardiograph for measuring ECG |
Nasal CO2 Sample Line | Salter Labs | REF 4000 | Latex free nasal cannula for sampling expired air |
Hemorrhage is the leading cause of trauma-related deaths, partly because early diagnosis of the severity of blood loss is difficult. Assessment of hemorrhaging patients is difficult because current clinical tools provide measures of vital signs that remain stable during the early stages of bleeding due to compensatory mechanisms. Consequently, there is a need to understand and measure the total integration of mechanisms that compensate for reduced circulating blood volume and how they change during ongoing progressive hemorrhage. The body's reserve to compensate for reduced circulating blood volume is called the 'compensatory reserve'. The compensatory reserve can be accurately evaluated with real-time measurements of changes in the features of the arterial waveform measured with the use of a high-powered computer. Lower Body Negative Pressure (LBNP) has been shown to simulate many of the physiological responses in humans associated with hemorrhage, and is used to study the compensatory response to hemorrhage. The purpose of this study is to demonstrate how compensatory reserve is assessed during progressive reductions in central blood volume with LBNP as a simulation of hemorrhage.
Hemorrhage is the leading cause of trauma-related deaths, partly because early diagnosis of the severity of blood loss is difficult. Assessment of hemorrhaging patients is difficult because current clinical tools provide measures of vital signs that remain stable during the early stages of bleeding due to compensatory mechanisms. Consequently, there is a need to understand and measure the total integration of mechanisms that compensate for reduced circulating blood volume and how they change during ongoing progressive hemorrhage. The body's reserve to compensate for reduced circulating blood volume is called the 'compensatory reserve'. The compensatory reserve can be accurately evaluated with real-time measurements of changes in the features of the arterial waveform measured with the use of a high-powered computer. Lower Body Negative Pressure (LBNP) has been shown to simulate many of the physiological responses in humans associated with hemorrhage, and is used to study the compensatory response to hemorrhage. The purpose of this study is to demonstrate how compensatory reserve is assessed during progressive reductions in central blood volume with LBNP as a simulation of hemorrhage.
Hemorrhage is the leading cause of trauma-related deaths, partly because early diagnosis of the severity of blood loss is difficult. Assessment of hemorrhaging patients is difficult because current clinical tools provide measures of vital signs that remain stable during the early stages of bleeding due to compensatory mechanisms. Consequently, there is a need to understand and measure the total integration of mechanisms that compensate for reduced circulating blood volume and how they change during ongoing progressive hemorrhage. The body's reserve to compensate for reduced circulating blood volume is called the 'compensatory reserve'. The compensatory reserve can be accurately evaluated with real-time measurements of changes in the features of the arterial waveform measured with the use of a high-powered computer. Lower Body Negative Pressure (LBNP) has been shown to simulate many of the physiological responses in humans associated with hemorrhage, and is used to study the compensatory response to hemorrhage. The purpose of this study is to demonstrate how compensatory reserve is assessed during progressive reductions in central blood volume with LBNP as a simulation of hemorrhage.