RESUMO
BACKGROUND: To study central hypovolemia in humans, lower body negative pressure (LBNP) is a recognized alternative to blood removal (HEM). While LBNP mimics the cardiovascular responses of HEM in baboons, similarities in hemostatic responses to LBNP and HEM remain unknown in this species. METHODS: Thirteen anesthetized baboons were exposed to progressive hypovolemia by HEM and, four weeks later, by LBNP. Hemostatic activity was evaluated by plasma markers, thromboelastography (TEG), flow cytometry, and platelet aggregometry at baseline (BL), during and after hypovolemia. RESULTS: BL values were indistinguishable for most parameters although platelet count, maximal clot strength (MA), protein C, thrombin anti-thrombin complex (TAT), thrombin activatable fibrinolysis inhibitor (TAFI) activity significantly differed between HEM and LBNP. Central hypovolemia induced by either method activated coagulation; TEG R-time decreased and MA increased during and after hypovolemia compared to BL. Platelets displayed activation by flow cytometry; platelet count and functional aggregometry were unchanged. TAFI activity and protein, Factors V and VIII, vWF, Proteins C and S all demonstrated hemodilution during HEM and hemoconcentration during LBNP, whereas tissue plasminogen activator (tPA), plasmin/anti-plasmin complex, and plasminogen activator inhibitor-1 did not. Fibrinolysis (TEG LY30) was unchanged by either method; however, at BL, fibrinolysis varied greatly. Post-hoc analysis separated baboons into low-lysis (LY30 <2%) or high-lysis (LY30 >2%) whose fibrinolytic state matched at both HEM and LBNP BL. In high-lysis, BL tPA and LY30 correlated strongly (r = 0.95; P<0.001), but this was absent in low-lysis. In low-lysis, BL TAFI activity and tPA correlated (r = 0.88; P<0.050), but this was absent in high-lysis. CONCLUSIONS: Central hypovolemia induced by either LBNP or HEM resulted in activation of coagulation; thus, LBNP is an adjunct to study hemorrhage-induced pro-coagulation in baboons. Furthermore, this study revealed a subset of baboons with baseline hyperfibrinolysis, which was strongly coupled to tPA and uncoupled from TAFI activity.
Assuntos
Fibrinólise , Hemorragia/complicações , Hemostasia , Hipovolemia/tratamento farmacológico , Hipovolemia/fisiopatologia , Pressão Negativa da Região Corporal Inferior/efeitos adversos , Animais , Masculino , PapioRESUMO
BACKGROUND: This study determined the long-term effects of prolonged hypotension (PH) on liver, muscle, and kidney dysfunction. The hypothesis was that longer duration of PH after hemorrhage will result in greater organ dysfunction. METHODS: Baboons were sedated and hemorrhaged (30% blood volume). Systolic blood pressure greater than 80 mm Hg was maintained for 1 hour (1 hr-PH; n = 5), 2 hours (2 hr-PH; n = 5), or 3 hours (3 hr-PH; n = 5). After PH, hemorrhage volume was replaced. Animals were recovered and monitored for 21 days. Control animals were hemorrhaged and immediately resuscitated (0 hr-PH, n = 3). Data are Mean ± Standard Deviation, and analyzed by 2-way repeated measures ANOVA and Holm-Sidak test. RESULTS: Hemorrhage resulted in mild hypotension. Minimal resuscitation was required during the hypotensive phase, and survival rate was 100%. Significant increases (p < 0.001) in alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, and lactate dehydrogenase occurred on Day 1 after PH, and were significantly greater (p < 0.001) in the 2 hr- and 3 hr-PH groups than the 0 hr-PH group. Maximum alanine aminotransferase levels (U/L) were 140 ± 56 (0 hr-PH), 170 ± 130 (1 hr-PH), 322 ± 241 (2 hr-PH), and 387 ± 167 (3 hr-PH). Maximum aspartate aminotransferase levels (U/L) were 218 ± 44 (0 hr-PH), 354 ± 219 (1 hr-PH), 515 ± 424 (2 hr-PH), and 711 ± 278 (3 hr-PH). Maximum creatine phosphokinase values (U/L) were 7834 ± 3681 (0 hr-PH), 24336 ± 22268 (1 hr-PH), 50494 ± 67653 (2 hr-PH), and 59857 ± 32408 (3 hr-PH). Maximum lactic acid dehydrogenase values (U/L) were 890 ± 396 (0 hr-PH), 2055 ± 1520 (1 hr-PH), 3992 ± 4895 (2 hr-PH), and 4771 ± 1884 (3 hr-PH). Plasma creatinine and blood urea nitrogen were unaffected by PH (p > 0.10). CONCLUSION: These results indicate that PH up to 3 hours in duration results in transient liver and muscle dysfunction that was most severe after 2 hr-PH and 3 hr-PH. Prolonged hypotension produced minimal effects on the kidney. LEVEL OF EVIDENCE: Basic science research, Level of evidence not required for basic science research.
Assuntos
Hemorragia/complicações , Hipotensão/etiologia , Hipotensão/fisiopatologia , Rim/fisiopatologia , Fígado/fisiopatologia , Músculos/fisiopatologia , Animais , Masculino , Papio , Fatores de TempoRESUMO
BACKGROUND: The measurement of the body's capacity to compensate for reduced blood volume can be assessed with a compensatory reserve measurement (CRM). The CRM, which is calculated from changes in features of the arterial waveform, represents the integration of compensatory mechanisms during states of low tissue perfusion and oxygenation, such as hemorrhage. This study was designed to test the hypothesis that pain which activates compensatory mechanisms and analgesia that result in reduced blood pressure are associated with lower compensatory reserve. This study evaluated CRM in obstetric patients during labor as pain intensity increased from no pain to severe pain and compared CRM before and after epidural anesthesia. METHODS: CRM was calculated from a finger pulse oximeter placed on the patient's index finger and connected to the DataOx monitor in healthy pregnant women (n = 20) before and during the active labor phase of childbirth. RESULTS: As pain intensity, based on an 11-point scale (0, no pain; 10, worst pain), increased from 0 to 8.4 ± 0.9 (mean ± SD), CRM was not affected (81 ± 10% to 82 ± 13%). Before analgesia, CRM was 84 ± 10%. CRM at 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, and 60 minutes after analgesia was 82 ± 11%, 83 ± 14%, 83 ± 15%, 86 ± 12%, 89 ± 9%, and 87 ± 10%, respectively. There was a transient 2% reduction followed by a 5% increase in CRM from before to after epidural anesthesia (p = 0.048). Pain scores before and after analgesia were 7 ± 2 and 1 ± 1, respectively (p < 0.001). CONCLUSION: These results indicate that pain and analgesia contribute minimally, but independently to the reduction in compensatory reserve associated with trauma and hemorrhage. As such, our findings suggest that analgesia can be safely administered on the battlefield while maintaining the maximal capacity of mechanisms to compensate for blood loss. LEVEL OF EVIDENCE: Diagnostic study, level II.
Assuntos
Trabalho de Parto , Medição da Dor/métodos , Adolescente , Adulto , Algoritmos , Anestesia Epidural , Pressão Sanguínea , Feminino , Frequência Cardíaca , Humanos , Monitorização Fisiológica , Oximetria , Manejo da Dor , Gravidez , Resultado da Gravidez , Taxa RespiratóriaRESUMO
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.
Assuntos
Hemorragia , Modelos Teóricos , Pressão Sanguínea , Volume Sanguíneo , Frequência Cardíaca , Humanos , Pressão Negativa da Região Corporal InferiorRESUMO
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.
Assuntos
Transfusão de Sangue , Hidratação , Fotopletismografia , Dengue Grave/fisiopatologia , Dengue Grave/terapia , Algoritmos , Pressão Sanguínea , Criança , Hemodinâmica , Humanos , Masculino , Resultado do TratamentoRESUMO
INTRODUCTION: As technological advances allow for the development of more sophisticated measurement of the mechanisms that contribute to compensation for loss of circulating blood volume such as hemorrhage, it is important to compare the discriminative ability of these new measures to standard vital signs and other new physiologic metrics of interest. The purpose of this study was to compare the discriminative ability of the following three measures to predict the onset of hemodynamic decompensation: peripheral perfusion index (PPI), pulse pressure variability (PPV), and the compensatory reserve index (CRI). MATERIALS AND METHODS: There were 51 healthy participants who underwent a progressive simulated hemorrhage to induce central hypovolemia by lower body negative pressure (LBNP). The least-squares means and 95% confidence intervals for each measure were reported by LBNP level and stratified by tolerance status (high tolerance vs. low tolerance). Generalized estimating equations were used to perform repeated measures logistic regression analysis by regressing the onset of hemodynamic decompensation on each of the vital signs of interest. These probabilities were used to calculate sensitivity, specificity, and receiver-operating characteristic area under the curve (ROCAUC) for PPI, PPV, and CRI. RESULTS: Compared with both PPV (ROCAUCâ=â0.79) and PPI (0.56), the CRI (0.90) had superior discriminative ability (Pâ≤â0.0001) to predict the onset of hemodynamic decompensation. This included higher sensitivity (0.86 vs. 0.78 and 0.71) and specificity (0.78 vs. 0.69 and 0.29) for the CRI compared with PPV and PPI, respectively. Further, CRI was the only measure with mean predicted probabilities of the onset of hemodynamic decompensation that progressively increased as the level of simulated hemorrhage increased. DISCUSSION: There are two potential rationales for why the CRI had superior discriminative ability to predict hemodynamic decompensation. First, the CRI more accurately predicted the onset of hemodynamic decompensation at all levels of simulated hemorrhage, but especially at lower levels of hemorrhage. Second, the CRI was better able to differentiate high versus low tolerant participants. CONCLUSION: Consistent with previous research, the CRI had superior discriminative ability to predict the onset of hemodynamic decompensation. For those patients at greatest risk for developing impending circulatory shock, identifying the most sensitive and specific measures of the onset of hemodynamic decompensation is critical for both the early recognition and implementation of life-saving interventions.
Assuntos
Pressão Sanguínea/fisiologia , Volume Sanguíneo/fisiologia , Cardiologia/métodos , Hemorragia/diagnóstico , Hipovolemia/diagnóstico , Adulto , Área Sob a Curva , Feminino , Frequência Cardíaca/fisiologia , Hemodinâmica , Humanos , Análise dos Mínimos Quadrados , Pressão Negativa da Região Corporal Inferior , Masculino , Perfusão , Probabilidade , Choque/prevenção & controle , Volume Sistólico/fisiologia , Adulto JovemRESUMO
INTRODUCTION: We hypothesized that repeated respiratory straining maneuvers (repeated SM) designed to elevate arterial BPs (arterial baroreceptor loading) would acutely increase baroreflex responses. METHODS: We tested this hypothesis by measuring cardiac baroreflex responses to carotid baroreceptor stimulation (neck pressures), and changes in heart rate and diastolic BP after reductions in BP induced by a 15-s Valsalva maneuver in 10 female and 10 male subjects at 1, 3, 6, and 24 h after performing repeated SM. Baroreflex responses were also measured in each subject at 1, 3, 6, and 24 h at the same time on a separate day without repeated SM (control) in a randomized, counter-balanced cross-over experimental design. RESULTS: There was no statistical difference in carotid-cardiac and peripheral vascular baroreflex responses measured across time following repeated SM compared with the control condition. Integrated cardiac baroreflex response (deltaHR/ deltaSBP) measured during performance of a Valsalva maneuver was increased by approximately 50% to 1.1 +/- 0.2 bpm x mm Hg(-1) at 1 h and 1.0 +/- 0.1 bpm x mm Hg(-1) at 3 h following repeated SM compared with the control condition (0.7 +/- 0.1 bpm x mm Hg(-1) at both 1 and 3 h, respectively). However, integrated cardiac baroreflex response after repeated SM returned to control levels at 6 and 24 h after training. These responses did not differ between men and women. CONCLUSIONS: Our results are consistent with the notion that arterial baroreceptor loading induced by repeated SM increased aortic, but not carotid, cardiac baroreflex responses for as long as 3 h after repeated SM. We conclude that repeated SM increases cardiac baroreflex responsiveness which may provide patients, astronauts, and high-performance aircraft pilots with protection from development of orthostatic hypotension.
Assuntos
Barorreflexo/fisiologia , Manobra de Valsalva , Adulto , Medicina Aeroespacial , Pressão Sanguínea , Feminino , Frequência Cardíaca , Humanos , Hipotensão Ortostática/prevenção & controle , Masculino , Pressorreceptores/fisiologia , Voo EspacialRESUMO
Lower body negative pressure (LBNP), a model of hemorrhage (Hem), shifts blood to the legs and elicits central hypovolemia. This study compared responses to LBNP and actual Hem in sedated baboons. Arterial pressure, pulse pressure (PP), central venous pressure (CVP), heart rate, stroke volume (SV), and +dP/dt were measured. Hem steps were 6.25%, 12.5%, 18.75%, and 25% of total estimated blood volume. Shed blood was returned, and 4 wk after Hem, the same animals were subjected to four LBNP levels which elicited equivalent changes in PP and CVP observed during Hem. Blood gases, hematocrit (Hct), hemoglobin (Hb), plasma renin activity (PRA), vasopressin (AVP), epinephrine (EPI), and norepinephrine (NE) were measured at baseline and maximum Hem or LBNP. LBNP levels matched with 6.25%, 12.5%, 18.75%, and 25% hemorrhage were -22 ± 6, -41 ± 7, -54 ± 10, and -71 ± 7 mmHg, respectively (mean ± SD). Hemodynamic responses to Hem and LBNP were similar. SV decreased linearly such that 25% Hem and matching LBNP caused a 50% reduction in SV. Hem caused a decrease in Hct, Hb, and central venous oxygen saturation (ScvO2). In contrast, LBNP increased Hct and Hb, while ScvO2 remained unchanged. Hem caused greater elevations in AVP and NE than LBNP, while PRA, EPI, and other hematologic indexes did not differ between studies. These results indicate that while LBNP does not elicit the same effect on blood cell loss as Hem, LBNP mimics the integrative cardiovascular response to Hem, and validates the use of LBNP as an experimental model of central hypovolemia associated with Hem.
Assuntos
Hemodinâmica , Hemorragia/fisiopatologia , Hipovolemia/fisiopatologia , Pressão Negativa da Região Corporal Inferior , Extremidade Inferior/irrigação sanguínea , Animais , Biomarcadores/sangue , Volume Sanguíneo , Modelos Animais de Doenças , Hemorragia/sangue , Hemorragia/etiologia , Hipovolemia/sangue , Hipovolemia/etiologia , Masculino , Papio , Fluxo Sanguíneo Regional , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
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.
Assuntos
Técnicas de Apoio para a Decisão , Serviço Hospitalar de Emergência , Hemorragia/diagnóstico , Algoritmos , Hemodinâmica/fisiologia , Hemorragia/fisiopatologia , Humanos , Monitorização Fisiológica , Fatores de Tempo , Sinais Vitais/fisiologiaRESUMO
OBJECTIVE: Increased negative intrathoracic pressure during spontaneous inspiration through an impedance threshold device (ITD) causes elevated arterial blood pressure in humans. This study was performed to determine whether the acute increase in blood pressure induced by breathing through an ITD is associated with increased stroke volume and cardiac output. DESIGN: Randomized, blinded, controlled trial. SETTING: Laboratory. SUBJECTS: Ten women and ten men. INTERVENTIONS: We measured hemodynamic and respiratory responses during two separate ITD conditions: 1) breathing through a face mask with an ITD (impedance of 6 cm H2O [0.59 kPa]) and 2) breathing through the same face mask with a sham ITD (control). Stroke volume was measured by thoracic bioimpedance. MEASUREMENTS AND MAIN RESULTS: Compared with the control condition, ITD produced higher stroke volume (124 +/- 3 vs. 137 +/- 3 mL; p = .013), heart rate (63 +/- 3 vs. 68 +/- 3 beats/min; p = .049), cardiac output (7.69 vs. 9.34 L/min; p = .001), and systolic blood pressure (115 +/- 2 to 122 +/- 2 mm Hg [15.33 +/- 0.3 to 16.26 +/- 0.3 kPa]; p = .005) without affecting expired minute ventilation (6.2 +/- 0.4 to 6.5 +/- 0.4 L/min; p = .609). CONCLUSIONS: Breathing with an ITD at relatively low impedance increases systolic blood pressure by increasing stroke volume and cardiac output. The ITD may provide short-term protection against cardiovascular collapse induced by orthostatic stress or hemorrhage.
Assuntos
Pressão Sanguínea , Cardiografia de Impedância/instrumentação , Frequência Cardíaca , Máscaras , Respiração , Adulto , Feminino , Humanos , Masculino , Volume SistólicoRESUMO
We were interested in a therapeutic device designed to increase carotid-cardiac baroreflex sensitivity (BRS) since high BRS is associated with a lower risk for development of hypotension in humans with experimentally-induced central hypovolemia. We hypothesized that spontaneous breathing through an impedance threshold device (ITD) designed to increase negative intrathoracic pressure during inspiration and elevate arterial blood pressure would acutely increase BRS in humans. We tested this hypothesis by measuring heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressures, and carotid-cardiac BRS in 10 female and 10 male subjects breathing through a face mask at three separate ITD conditions: (a) 6 cm H(2)O; (b) 12 cm H(2)O; and (c) a control (0 cm H(2)O). HR was increased (P = 0. 013) from 64 +/- 3 bpm during control to 68 +/- 3 bpm at 6 cm H(2)O ITD and 71 +/- 4 bpm at 12 cm H(2)O ITD breathing conditions. During ITD breathing, BRS was not altered but responses were shifted to higher arterial pressures. However, SBP and DBP were elevated for both the 6 and 12 cm H(2)O conditions compared to the 0 cm H(2)O condition, but returned to control (sham) levels by 30 minutes after cessation of ITD breathing. There were no gender effects for BRS or any hemodynamic responses to breathing through the ITD. We conclude that breathing with inspiratory impedance at relatively low pressures can increase baseline arterial blood pressure, i. e., reset the operational point for SBP on the baroreflex stimulus-response relationship, in healthy subjects. This resetting of the cardiac baroreflex may represent a mechanism that allows blood pressure to increase without a reflex-mediated reduction in HR.