The compensatory reserve index predicts recurrent shock in patients with severe dengue.

BACKGROUND: Dengue shock syndrome (DSS) is one of the major clinical phenotypes of severe dengue. It is defined by significant plasma leak, leading to intravascular volume depletion and eventually cardiovascular collapse. The compensatory reserve Index (CRI) is a new physiological parameter, derived from feature analysis of the pulse arterial waveform that tracks real-time changes in central volume. We investigated the utility of CRI to predict recurrent shock in severe dengue patients admitted to the ICU. METHODS: We performed a prospective observational study in the pediatric and adult intensive care units at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. Patients were monitored with hourly clinical parameters and vital signs, in addition to continuous recording of the arterial waveform using pulse oximetry. The waveform data was wirelessly transmitted to a laptop where it was synchronized with the patient's clinical data. RESULTS: One hundred three patients with suspected severe dengue were recruited to this study. Sixty-three patients had the minimum required dataset for analysis. Median age was 11 years (IQR 8-14 years). CRI had a negative correlation with heart rate and moderate negative association with blood pressure. CRI was found to predict recurrent shock within 12 h of being measured (OR 2.24, 95% CI 1.54-3.26), P < 0.001). The median duration from CRI measurement to the first recurrent shock was 5.4 h (IQR 2.9-6.8). A CRI cutoff of 0.4 provided the best combination of sensitivity and specificity for predicting recurrent shock (0.66 [95% CI 0.47-0.85] and 0.86 [95% CI 0.80-0.92] respectively). CONCLUSION: CRI is a useful non-invasive method for monitoring intravascular volume status in patients with severe dengue.

Comparison of compensatory reserve during lower-body negative pressure and hemorrhage in nonhuman primates.

Compensatory reserve was measured in baboons (n = 13) during hemorrhage (Hem) and lower-body negative pressure (LBNP) using a machine-learning algorithm developed to estimate compensatory reserve by detecting reductions in central blood volume during LBNP. The algorithm calculates compensatory reserve index (CRI) from normovolemia (CRI = 1) to cardiovascular decompensation (CRI = 0). The hypothesis was that Hem and LBNP will elicit similar CRI values and that CRI would have higher specificity than stroke volume (SV) in predicting decompensation. Blood was removed in four steps: 6.25%, 12.5%, 18.75%, and 25% of total blood volume. Four weeks after Hem, the same animals were subjected to four levels of LBNP that was matched on the basis of their central venous pressure. Data (mean ± 95% confidence interval) indicate that CRI decreased (P < 0.001) from baseline during Hem (0.69 ± 0.10, 0.57 ± 0.09, 0.36 ± 0.10, 0.16 ± 0.08, and 0.08 ± 0.03) and LBNP (0.76 ± 0.05, 0.66 ± 0.08, 0.36 ± 0.13, 0.23 ± 0.11, and 0.14 ± 0.09). CRI was not different between Hem and LBNP (P = 0.20). Linear regression analysis between Hem CRI and LBNP CRI revealed a slope of 1.03 and a correlation coefficient of 0.96. CRI exhibited greater specificity than SV in both Hem (92.3 vs. 82.1) and LBNP (94.8 vs. 83.1) and greater ROC AUC in Hem (0.94 vs. 0.84) and LBNP (0.94 vs. 0.92). These data support the hypothesis that Hem and LBNP elicited the same CRI response, suggesting that measurement of compensatory reserve is superior to SV as a predictor of cardiovascular decompensation.

Respiratory pump contributes to increased physiological reserve for compensation during simulated haemorrhage.

Intrathoracic pressure regulation (IPR) represents a therapy for increasing systemic circulation through the creation of negative intrathoracic pressure. We hypothesized that using this 'respiratory pump' effect would slow the diminution of the physiological reserve to compensate during progressive reductions in central blood volume. The compensatory reserve index (CRI) algorithm was used to measure the proportion (from 100 to 0%) of reserve capacity that remained to compensate for central volume loss before the onset of cardiovascular decompensation. Continuous analog recordings of arterial waveforms were extracted from data files of seven healthy volunteers. Subjects had previously participated in experiments designed to induce haemodynamic decompensation (presyncope) by progressive reduction in central blood volume using graded lower-body negative pressure. The lower-body negative pressure protocol was completed while breathing spontaneously through a standard medical face mask without (placebo) and with a resistance (approximately -7 cmH2O; active IPR) applied during inspiration. At the onset of presyncope in the placebo conditions, CRI was smaller than the CRI observed at the same time point in the active IPR conditions. The CRI at the onset of presyncope during active IPR (0.08 ± 0.01) was similar to the CRI at presyncope with placebo. Kaplan-Meier and log rank tests indicated that CRI survival curves were shifted to the right by active IPR. Optimizing the respiratory pump contributed a small but significant effect of increasing tolerance to progressive reductions in central blood volume by extending the compensatory reserve.

A sensitive shock index for real-time patient assessment during simulated hemorrhage.

BACKGROUND: Shock index [SI = the ratio of heart rate (HR) to systolic arterial pressure (SAP)] is a metric used to diagnose patients at risk of impending hemorrhagic shock. We hypothesized that a metric called the compensatory reserve index (CRI), derived using computer modeling with continuous feature extraction from arterial waveforms, would provide an earlier indicator of cardiovascular instability than SI during progressive central hypovolemia. METHODS: There were 15 subjects (men = 8; women = 7) who underwent progressive reduction in central blood volume induced by lower body negative pressure (LBNP) until SAP < 90 mmHg. CRI was normalized on a scale of 1 (normovolemia) to 0 (circulatory volume at which instability occurs) and displayed on a colored bar. The times at which the CRI equaled 0.6 (threshold of green to amber) or 0.3 (threshold of amber to red) were compared to a clinical threshold of SI > or = 0.9. RESULTS: A SI > or = 0.9 required 22.4 +/- 6.2 min (95% CI = 19 to 25.8 min). CRI reached 0.6 (amber) at 12.5 +/- 4.9 min (95% CI = 9.8 to 15.3 min) when SI = 0.61 +/- 0.03, and became 0.3 (red) at 20.3 +/- 5.1 min (95% CI = 17.5 to 23.1 min) when SI = 0.81 +/- 1.4. CONCLUSIONS: CRI provided a significantly earlier indicator of impending hemodynamic decompensation than SI > or = 0.9 during progressive LBNP. These results support the notion that the CRI represents an improved 'shock index' as an indicator of impending hemorrhagic shock compared to standard vital signs.

Emerging technologies for pediatric and adult trauma care.

PURPOSE OF REVIEW: Current Emergency Medical Service protocols rely on provider-directed care for evaluation, management and triage of injured patients from the field to a trauma center. New methods to quickly diagnose, support and coordinate the movement of trauma patients from the field to the most appropriate trauma center are in development. These methods will enhance trauma care and promote trauma system development. RECENT FINDINGS: Recent advances in machine learning, statistical methods, device integration and wireless communication are giving rise to new methods for vital sign data analysis and a new generation of transport monitors. These monitors will collect and synchronize exponentially growing amounts of vital sign data with electronic patient care information. The application of advanced statistical methods to these complex clinical data sets has the potential to reveal many important physiological relationships and treatment effects. SUMMARY: Several emerging technologies are converging to yield a new generation of smart sensors and tightly integrated transport monitors. These technologies will assist prehospital providers in quickly identifying and triaging the most severely injured children and adults to the most appropriate trauma centers. They will enable the development of real-time clinical support systems of increasing complexity, able to provide timelier, more cost-effective, autonomous care.

Low postnatal CRI values are associated with the need for ECMO in newborns with CDH.

INTRODUCTION: Accurate, real-time technology is needed to predict which newborns with congenital diaphragmatic hernia (CDH) will require ECMO. The Compensatory Reserve Index (CRI) is a noninvasive monitoring technology that continuously trends an individual's capacity to compensate from normovolemia (CRI = 1) to decompensation (CRI = 0). We hypothesized that postnatal CRI values would be lower in CDH newborns that required ECMO than those who did not require ECMO. METHODS: Newborns with a CDH were prospectively monitored with a CipherOx® CRI M1 device. We compared CRI values from delivery to ECMO (ECMO group) versus delivery to clinical stabilization (non-ECMO group). RESULTS: Postnatal CRI values were available from 26 newborns. Eight underwent ECMO within 33 h of delivery, and median CRI prior to ECMO was 0.068 (IQR: 0.057, 0.078). Eighteen did not require ECMO. Median CRI from birth to 48 h was 0.112 (IQR: 0.082, 0.15). CRI values were significantly lower in newborns that required ECMO versus those who did not (p = 0.0035). Postnatal CRI had the highest AUC (0.85) compared to other prenatal prognostic measures. CONCLUSION: Humans from newborns to adults share elemental features of the pulsatile waveform that are associated with progression to decompensation. CRI may be helpful when deciding when to initiate ECMO. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Diagnostic test.

Development of a Non-invasive Cerebrovascular Status Algorithm to Estimate Cerebral Perfusion Pressure and Intracranial Pressure in a Porcine Model of Focal Brain Injury.

Background: New tools for diagnosis, monitoring, and treatment of elevated intracranial pressure (ICP) or compromised cerebral perfusion pressure (CPP) are urgently needed to improve outcomes after brain injury. Previous success in applying advanced data analytics to build precision monitors based on large, noisy sensor datasets suggested applying the same approach to monitor cerebrovascular status. In these experiments, a new algorithm was developed to estimate ICP and CPP using the arterial pressure waveform. Methods: Sixty-five porcine subjects were subjected to a focal brain injury to simulate a mass lesion with elevated ICP. The arterial pressure waveform and the measured ICP from these subjects during injury and treatment were then utilized to develop and calibrate an ICP and CPP estimation algorithm. These estimation algorithms were then subsequently evaluated on 14 new subjects. Results: The root mean square difference between actual ICP and estimated ICP was 2.0961 mmHg. The root mean square difference between the actual CPP and the estimated CPP was 2.6828 mmHg. Conclusion: A novel ICP or CPP monitor based on the arterial pressure signal produced a very close approximation to actual measured ICP and CPP and warrants further evaluation.

Noninvasive monitoring of physiologic compromise in acute appendicitis: New insight into an old disease.

INTRODUCTION: Physiologic compromise in children with acute appendicitis has heretofore been difficult to measure. We hypothesized that the Compensatory Reserve Index (CRI), a novel adjunctive cardiovascular status indicator, would be low for children presenting with acute appendicitis in proportion to their physiological compromise, and that CRI would rise with fluid resuscitation and surgical management of their disease. METHODS: Ninety-four children diagnosed with acute appendicitis were monitored with a CipherOx CRI™ M1 pulse oximeter (Flashback Technologies Inc., Boulder, CO). For clarity, CRI=1 indicates supine normovolemia, CRI=0 indicates hemodynamic decompensation (systolic blood pressure<80mmHg), and CRI values between 1 and 0 indicate the proportion of volume reserve remaining before collapse. Results are presented as counts with proportion (%), or mean with 95% confidence interval (CI). RESULTS: Mean age was 11years old (95% CI: 10-12), and 49 (52%) of the children were male. Fifty-four (57%) had nonperforated appendicitis and 40 (43%) had perforated appendicitis. Mean initial CRI was significantly higher in those with nonperforated appendicitis compared to those with perforated appendicitis (0.57, 95% CI: 0.52-0.63 vs. 0.36, 95% CI: 0.29-0.43; P<0.001). The significant differences in mean CRI values between the two groups remained throughout the course of treatment, but lost its significance at 2h after surgery (0.63, 95% CI: 0.57-0.70 vs. 0.53, 95% CI: 0.46-0.61; P=0.05). CONCLUSION: Low CRI values in children with perforated appendicitis are indicative of their lower reserve capacity owing to peritonitis and hypovolemia. CRI offers a real-time, noninvasive adjunctive tool to monitor tolerance to volume loss in children. LEVEL OF EVIDENCE: Study of diagnostic test; Level of evidence: Level III.

Validation of a noninvasive monitor to continuously trend individual responses to hypovolemia.

BACKGROUND: Humans are able to compensate for significant blood loss with little change in traditional vital signs, limiting early detection and intervention. We hypothesized that the Compensatory Reserve Index (CRI), a new hemodynamic parameter that trends changes in intravascular volume relative to the individual patient's response to hypovolemia, would accurately trend each subject's progression from normovolemia to decompensation (systolic blood pressure < 80) and back to normovolemia in humans. METHODS: Men and women, ages 19 years to 36 years, underwent stepwise (~333 mL aliquot) removal and replacement of 20% blood volume (men, 15 mL/kg; women, 13 mL/kg) via a large bore intravenous (i.v.) line. During each experiment, subjects were monitored with four CipherOx CRI Tablets. Withdrawn blood was reinfused at the end of each experiment. RESULTS: Forty-two subjects (24 men; 18 women) were enrolled in the study, of which 32 completed the protocol. Seven subjects became symptomatic and collapsed (systolic blood pressure < 80), six never achieving maximum blood loss; each was rescued with a saline infusion followed by reinfusion of their stored blood. The mean CRI at baseline for all 42 subjects was 0.9 ± 0.04. The mean CRI for the 32 subjects while asymptomatic at maximum blood loss was 0.611 ± 0.028. For the asymptomatic subjects, the average blood loss volume was 1018 mL ± 286 mL. In comparison, the mean CRI at maximum blood loss for the seven subjects who collapsed was 0.15 ± 0.007 and their average blood loss volume was 860 ± 183 mL. Mean CRI after reinfusion of blood was 0.89 ± 0.02. In addition symptomatic subjects demonstrated three times larger average decrease in CRI per liter of blood removed, 0.85 versus 0.28 for asymptomatic subjects. CONCLUSION: CRI trends change in intravascular volume relative to an individual's response to hypovolemia and is sensitive to the differing risks associated with individuals' differing tolerance to volume loss. LEVEL OF EVIDENCE: Prognostic study, level II.

Compensatory Reserve for Early and Accurate Prediction of Hemodynamic Compromise: Case Studies for Clinical Utility in Acute Care and Physical Performance.

BACKGROUND: Humans are able to compensate for significant loss of their circulating blood volume, allowing vital signs to remain relatively stable until compensatory mechanisms are overwhelmed. The authors present several clinical and performance case studies in an effort to demonstrate real-time measurements of an individual's reserve to compensate for acute changes in circulating blood volume. This measurement is referred to as the Compensatory Reserve Index (CRI). METHODS: We identified seven clinical and two physical performance conditions relevant to military casualty and operational medicine as models of intravascular volume compromise. Retrospective analysis of photoplethysmogram (PPG) waveform features was used to calculate CRI, where 1 represents supine normovolemia and 0 represents hemodynamic decompensation. RESULTS: All cases had CRI values suggestive of volume compromise (<0.6) not otherwise evident by heart rate and systolic blood pressure. CRI decreased with reduced central blood volume and increased with restored volume (e.g., fluid resuscitation). CONCLUSION: The results from these case studies demonstrate that machine-learning techniques can be used to (1) identify a clinical or physiologic status of individuals through real-time measures of changes in PPG waveform features that result from compromise to circulating blood volume and (2) signal progression toward hemodynamic instability, with opportunity for early and effective intervention, well in advance of changes in traditional vital signs.

The Compensatory Reserve Index Following Injury: Results of a Prospective Clinical Trial.

INTRODUCTION: Humans are able to compensate for significant blood loss with little change in traditional vital signs. We hypothesized that an algorithm, which recognizes compensatory changes in photoplethysmogram (PPG) waveforms, could detect active bleeding and ongoing volume loss in injured patients. METHODS: Injured adults were prospectively enrolled at a level I trauma center. PPG data collection was conducted using a custom-made pulse oximeter. Waveform data were post-processed by an algorithm to calculate the compensatory reserve index (CRI), measured on a scale of 1 to 0, with 1 indicating fully compensated and 0 indicating no reserve, or decompensation. CRI was compared to clinical findings. RESULTS: Fifty patients were enrolled in the study; 3 had incomplete data, 3 had indeterminate bleeding, 12 were actively bleeding, and 32 were not bleeding. The mean initial CRI of bleeding patients was significantly lower compared with the non-bleeding patients (CRI 0.17, 95% CI = 0.13-0.22 vs. CRI 0.56, 95% CI = 0.49-0.62, P < 0.001). Using a cut-off of 0.21 had a sensitivity of 0.97 and specificity of 0.83 for identifying bleeding patients. CRI had a higher sensitivity than heart rate (75%), systolic blood pressure (63%), shock index (27%), base deficit (29%), lactate (80%), hemoglobin (50%), and hematocrit (50%). During ongoing bleeding, CRI decreased following fluid resuscitation, and conversely increased for patients who were not bleeding. CONCLUSIONS: A novel computational algorithm that recognizes subtle changes in PPG waveforms can quickly and noninvasively discern which patients are actively bleeding and continuing to bleed with high sensitivity and specificity in acutely injured patients.

The Effect of Passive Heat Stress and Exercise-Induced Dehydration on the Compensatory Reserve During Simulated Hemorrhage.

Compensatory reserve represents the proportion of physiological responses engaged to compensate for reductions in central blood volume before the onset of decompensation. We hypothesized that compensatory reserve would be reduced by hyperthermia and exercise-induced dehydration, conditions often encountered on the battlefield. Twenty healthy males volunteered for two separate protocols during which they underwent lower-body negative pressure (LBNP) to hemodynamic decompensation (systolic blood pressure <80 mm Hg). During protocol #1, LBNP was performed following a passive increase in core temperature of ∼1.2°C (HT) or a normothermic time-control period (NT). During protocol #2, LBNP was performed following exercise during which: fluid losses were replaced (hydrated), fluid intake was restricted and exercise ended at the same increase in core temperature as hydrated (isothermic dehydrated), or fluid intake was restricted and exercise duration was the same as hydrated (time-match dehydrated). Compensatory reserve was estimated with the compensatory reserve index (CRI), a machine-learning algorithm that extracts features from continuous photoplethysmograph signals. Prior to LBNP, CRI was reduced by passive heating [NT: 0.87 (SD 0.09) vs. HT: 0.42 (SD 0.19) units, P <0.01] and exercise-induced dehydration [hydrated: 0.67 (SD 0.19) vs. isothermic dehydrated: 0.52 (SD 0.21) vs. time-match dehydrated: 0.47 (SD 0.25) units; P <0.01 vs. hydrated]. During subsequent LBNP, CRI decreased further and its rate of change was similar between conditions. CRI values at decompensation did not differ between conditions. These results suggest that passive heating and exercise-induced dehydration limit the body's physiological reserve to compensate for further reductions in central blood volume.

State-of-the-art monitoring in treatment of dengue shock syndrome: a case series.

BACKGROUND: Early recognition and treatment of circulatory volume loss is essential in the clinical management of dengue viral infection. We hypothesized that a novel computational algorithm, originally developed for noninvasive monitoring of blood loss in combat casualties, could: (1) indicate the central volume status of children with dengue during the early stages of "shock"; and (2) track fluid resuscitation status. METHODS: Continuous noninvasive photoplethysmographic waveforms were collected over a 5-month period from three children of Thai ethnicity with clinical suspicion of dengue. Waveform data were processed by the algorithm to calculate each child's Compensatory Reserve Index, where 1 represents supine normovolemia and 0 represents the circulatory volume at which hemodynamic decompensation occurs. Values between 1 and 0 indicate the proportion of reserve remaining before hemodynamic decompensation. RESULTS: This case report describes a 7-year-old Thai boy, another 7-year-old Thai boy, and a 9-year-old Thai boy who exhibited signs and symptoms of dengue shock syndrome; all the children had secondary dengue virus infections, documented by serology and reverse transcriptase polymerase chain reaction. The three boys experienced substantial plasma leakage demonstrated by pleural effusion index >25, ascites, and >20 % hemoconcentration. They received fluid administered intravenously; one received a blood transfusion. All three boys showed a significantly low initial Compensatory Reserve Index (≥0.20), indicating a clinical diagnosis of "near shock". Following 5 days with fluid resuscitation treatment, their Compensatory Reserve Index increased towards "normovolemia" (that is, Compensatory Reserve Index >0.75). CONCLUSIONS: The results from these cases demonstrate a new variation in the diagnostic capability to manage patients with dengue shock syndrome. The findings shed new light on a method that can avoid possible adverse effects of shock by noninvasive measurement of a patient's compensatory reserve rather than standard vital signs or invasive diagnostic methods.

A noninvasive computational method for fluid resuscitation monitoring in pediatric burns: a preliminary report.

The fluid resuscitation needs of children with small area burns are difficult to predict. The authors hypothesized that a novel computational algorithm called the compensatory reserve index (CRI), calculated from the photoplethysmogram waveform, would correlate with percent total body surface area (%TBSA) and fluid administration in children presenting with ≤20% TBSA burns. The authors recorded photoplethysmogram waveforms from burn-injured children that were later processed by the CRI algorithm. A CRI of 1 represents supine normovolemia; a CRI of 0 represents the point at which a subject is predicted to experience hemodynamic decompensation. CRI values from the first 10 minutes of monitoring were compared to clinical data. Waveform data were available for 27 children with small to moderate sized burns (4-20 %TBSA). The average age was 6.3 ± 1.1 years, the average %TBSA was 10.4 ± 0.8%, and the average CRI was 0.36 ± 0.03. CRI inversely correlated with the %TBSA (P < .001). Twenty children were transferred with an average reported %TBSA of 16.5 ± 1.4%, which was significantly higher than the actual %TBSA (P < .001). CRI correlated better with actual %TBSA compared to reported %TBSA (P = .02). CRI correlated with the amount of fluid resuscitation given at the time of CRI measurement (P = .02) and was inversely related to total fluids given per 24 hours for children with adequate urine output (>0.5 ml/kg/hr) (P < .001). The CRI is decreased in children with small to moderate size burns, and correlates with %TBSA and fluid administration. This suggests that the CRI may be useful for fluid resuscitation guidance, warranting further study.

Individual-Specific, Beat-to-beat Trending of Significant Human Blood Loss: The Compensatory Reserve.

Current monitoring technologies are unable to detect early, compensatory changes that are associated with significant blood loss. We previously introduced a novel algorithm to calculate the Compensatory Reserve Index (CRI) based on the analysis of arterial waveform features obtained from photoplethysmogram recordings. In the present study, we hypothesized that the CRI would provide greater sensitivity and specificity to detect blood loss compared with traditional vital signs and other hemodynamic measures. Continuous noninvasive vital sign waveform data, including CRI, photoplethysmogram, heart rate, blood pressures, SpO2, cardiac output, and stroke volume, were analyzed from 20 subjects before, during, and after an average controlled voluntary hemorrhage of ∼1.2 L of blood. Compensatory Reserve Index decreased by 33% in a linear fashion across progressive blood volume loss, with no clinically significant alterations in vital signs. The receiver operating characteristic area under the curve for the CRI was 0.90, with a sensitivity of 0.80 and specificity of 0.76. In comparison, blood pressures, heart rate, SpO2, cardiac output, and stroke volume had significantly lower receiver operating characteristic area under the curve values and specificities for detecting the same volume of blood loss. Consistent with our hypothesis, CRI detected blood loss and restoration with significantly greater specificity than did other traditional physiologic measures. Single measurement of CRI may enable more accurate triage, whereas CRI monitoring may allow for earlier detection of casualty deterioration.

Detection of low-volume blood loss: compensatory reserve versus traditional vital signs.

BACKGROUND: Humans are able to compensate for low-volume blood loss with minimal change in traditional vital signs. We hypothesized that a novel algorithm, which analyzes photoplethysmogram (PPG) wave forms to continuously estimate compensatory reserve would provide greater sensitivity and specificity to detect low-volume blood loss compared with traditional vital signs. The compensatory reserve index (CRI) is a measure of the reserve remaining to compensate for reduced central blood volume, where a CRI of 1 represents supine normovolemia and 0 represents the circulating blood volume at which hemodynamic decompensation occurs; values between 1 and 0 indicate the proportion of reserve remaining. METHODS: Subjects underwent voluntary donation of 1 U (approximately 450 mL) of blood. Demographic and continuous noninvasive vital sign wave form data were collected, including PPG, heart rate, systolic blood pressure, cardiac output, and stroke volume. PPG wave forms were later processed by the algorithm to estimate CRI values. RESULTS: Data were collected from 244 healthy subjects (79 males and 165 females), with a mean (SD) age of 40.1 (14.2) years and mean (SD) body mass index of 25.6 (4.7). After blood donation, CRI significantly decreased in 92% (α = 0.05; 95% confidence interval [CI], 88-95%) of the subjects. With the use of a threshold decrease in CRI of 0.05 or greater for the detection of 1 U of blood loss, the receiver operating characteristic area under the curve was 0.90, with a sensitivity of 0.84 and specificity of 0.86. In comparison, systolic blood pressure (52%; 95% CI, 45-59%), heart rate (65%; 95% CI, 58-72%), cardiac output (47%; 95% CI, 40-54%), and stroke volume (74%; 95% CI, 67-80%) changed in fewer subjects, had significantly lower receiver operating characteristic area under the curve values, and significantly lower specificities for detecting the same volume of blood loss. CONCLUSION: Consistent with our hypothesis, CRI detected low-volume blood loss with significantly greater specificity than other traditional physiologic measures. These findings warrant further evaluation of the CRI algorithm in actual trauma settings. LEVEL OF EVIDENCE: Diagnostic study, level II.

Estimation of individual-specific progression to impending cardiovascular instability using arterial waveforms.

Trauma patients with "compensated" internal hemorrhage may not be identified with standard medical monitors until signs of shock appear, at which point it may be difficult or too late to pursue life-saving interventions. We tested the hypothesis that a novel machine-learning model called the compensatory reserve index (CRI) could differentiate tolerance to acute volume loss of individuals well in advance of changes in stroke volume (SV) or standard vital signs. Two hundred one healthy humans underwent progressive lower body negative pressure (LBNP) until the onset of hemodynamic instability (decompensation). Continuously measured photoplethysmogram signals were used to estimate SV and develop a model for estimating CRI. Validation of the CRI was tested on 101 subjects who were classified into two groups: low tolerance (LT; n = 33) and high tolerance (HT; n = 68) to LBNP (mean LBNP time: LT = 16.23 min vs. HT = 25.86 min). On an arbitrary scale of 1 to 0, the LT group CRI reached 0.6 at an average time of 5.27 ± 1.18 (95% confidence interval) min followed by 0.3 at 11.39 ± 1.14 min. In comparison, the HT group reached CRI of 0.6 at 7.62 ± 0.94 min followed by 0.3 at 15.35 ± 1.03 min. Changes in heart rate, blood pressure, and SV did not differentiate HT from LT groups. Machine modeling of the photoplethysmogram response to reduced central blood volume can accurately trend individual-specific progression to hemodynamic decompensation. These findings foretell early identification of blood loss, anticipating hemodynamic instability, and timely application of life-saving interventions.

Running on empty? The compensatory reserve index.

BACKGROUND: Hemorrhage is a leading cause of traumatic death. We hypothesized that state-of-the-art feature extraction and machine learning techniques could be used to discover, detect, and continuously trend beat-to-beat changes in arterial pulse waveforms associated with the progression to hemodynamic decompensation. METHODS: We exposed 184 healthy humans to progressive central hypovolemia using lower-body negative pressure to the point of hemodynamic decompensation (systolic blood pressure > 80 mm Hg with or without bradycardia). Initial models were developed using continuous noninvasive blood pressure waveform data. The resulting algorithm calculates a compensatory reserve index (CRI), where 1 represents supine normovolemia and 0 represents the circulatory volume at which hemodynamic decompensation occurs (i.e., "running on empty"). Values between 1 and 0 indicate the proportion of reserve remaining before hemodynamic decompensation-much like the fuel gauge of a car indicates the amount of fuel remaining in the tank. A CRI estimate is produced after the first 30 heart beats, followed by a new CRI estimate after each subsequent beat. RESULTS: The CRI model with a 30-beat window has an absolute difference between actual and expected time to decompensation of 0.1, with a SD of 0.09. The model distinguishes individuals with low tolerance to reduced central blood volume (i.e., those most likely to develop early shock) from those with high tolerance and are able to estimate how near or far an individual may be from hemodynamic decompensation. CONCLUSION: Machine modeling can quickly and accurately detect and trend central blood volume reduction in real time during the compensatory phase of hemorrhage as well as estimate when an individual is "running on empty" and will decompensate (CRI, 0), well in advance of meaningful changes in traditional vital signs.

Promoting early diagnosis of hemodynamic instability during simulated hemorrhage with the use of a real-time decision-assist algorithm.

BACKGROUND: This study aimed to test the hypothesis that the addition of a real-time decision-assist machine learning algorithm by emergency medical system personnel could shorten the time needed to identify an unstable patient during a hemorrhage profile as compared with vital sign information alone. METHODS: Fifty emergency medical team-paramedics from a large, urban fire department participated as subjects. Subjects viewed a monitor screen on two occasions as follows: (1) display of standard vital signs alone and (2) with the addition of an index (Compensatory Reserve Index) associated with estimated central blood volume status. The subjects were asked to push a computer key at any point in the sequence they believed the patient had become unstable based on information provided by the monitor screen. The average difference in time to identify hemodynamic instability between experimental and control groups was assessed by paired, two-tailed t test and reported with 95% confidence intervals (95% CI). RESULTS: The mean (SD) amount of time required to identify an unstable patient was 18.3 (4.1) minutes (95% CI, 17.2-19.4 minutes) without the algorithm and 10.7 (4.2) minutes (95% CI, 9.5-11.9 minutes) with the algorithm (p < 0.001). CONCLUSION: In a simulated patient encounter involving uncontrolled hemorrhage, the use of a monitor that estimates central blood volume loss was associated with early identification of impending hemodynamic instability. Physiologic monitors capable of early identification and estimation of the physiologic capacity to compensate for blood loss during hemorrhage may enable optimal guidance for hypotensive resuscitation. They may also help identify casualties benefitting from forward administration of plasma, antifibrinolytics and procoagulants in a remote damage-control resuscitation model.