Search

While physiological responses to hemorrhage are well-studied, hemorrhage is often accompanied by trauma, and it remains unclear how injury affects these responses. This study examined effects of extremity trauma on cardiorespiratory responses and survival to moderate (37%; H-37) or severe (50%; H-50) hemorrhage in rats. Transmitter and carotid catheter implantation, and extremity trauma (fibular fracture and muscle injury) were conducted 2 weeks, 24 hrs, and 90 min, respectively, prior to conscious hemorrhage. Mean arterial pressure (MAP) and heart rate (HR) (via telemetry), and respiration rate (RR), minute volume (MV), and tidal volume (TV) (via plethysmography) were measured throughout the 25 min hemorrhage and remainder of the 4 h observation period. There were four groups: 1) H-37, no trauma (NT; n=17); 2) H-37, extremity trauma (T, n=18); H-50, NT (n=20); and 4) H-50, T (n=20). For H-37, during and post-hemorrhage, T increased HR (P≤0.031) and MV (P ≤ 0.048) compared with NT-rats. During H-50, T increased HR (0.041) and MV (P=0.043). Post-hemorrhage, T increased MV (P=0.008), but decreased HR (P=0.007) and MAP (P=0.039). All cardiorespiratory differences between T and NT groups were intermittent. Importantly, both survival time (159.8 ± 78.2 min vs 211.9 ± 60.3 min; P = 0.022; mean ± SD) and percent survival (45% vs 80%; P = 0.048) were less in T vs NT-rats after H-50. Trauma interacts with physiological systems in a complex manner and no single cardiorespiratory measure was sufficiently altered to indicate that it alone could account for increased mortality after H-50.

A focus of combat casualty care research is to develop treatments for when full resuscitation after hemorrhage is delayed. However, few animal models exist to investigate such treatments. Given the kidney's susceptibility to ischemia, we determined how delayed resuscitation affects renal function in a model of traumatic shock. Rats were randomized into three groups: resuscitation after 1 h (ETH-1) or 2 h (ETH-2) of extremity trauma and hemorrhagic shock, and sham control. ETH was induced in anesthetized rats with muscle injury and fibula fracture, followed by pressure-controlled hemorrhage [mean arterial pressure (MAP) = 55 mmHg] for 1 or 2 h. Rats were then resuscitated with whole blood until MAP stabilized between 90 and 100 mmHg for 30 min. MAP, glomerular filtration rate (GFR), creatinine, blood gases, and fractional excretion of sodium (nFENa

Introduction Battlefield pain management changed markedly during the first 20 years of the Global War on Terror. Morphine, long the mainstay of combat analgesia, diminished in favor of fentanyl and ketamine for military pain control, but the options are not hemodynamically or psychologically equivalent. Understanding patterns of prehospital analgesia may reveal further opportunities for combat casualty care improvement. Materials and Methods Using Department of Defense Trauma Registry data for the Afghanistan conflict from 2005 to 2018, we examined 2,402 records of prehospital analgesia administration to assess temporal trends in medication choice and proportions receiving analgesia, including subanalysis of a cohort screened for an indication with minimal contraindication for analgesia. We further employed frequency matching to explore the presence of disparities in analgesia by casualty affiliation. Results Proportions of documented analgesia increased throughout the study period, from 0% in 2005 to 70.6% in 2018. Afghan casualties had the highest proportion of documented analgesia (53.0%), versus U.S. military (31.9%), civilian/other (23.3%), and non-U.S. military (19.3%). Fentanyl surpassed morphine in the frequency of administration in 2012. The median age of those receiving ketamine was higher (30 years) than those receiving fentanyl (26 years) or nonsteroidal anti-inflammatory drugs (23 years). Among the frequency-matched subanalysis, the odds ratio for ketamine administration with Afghan casualties was 1.84 (95% CI, 1.30-2.61). Conclusions We observed heterogeneity of prehospital patient care across patient affiliation groups, suggesting possible opportunities for improvement toward an overall best practice system. General increase in documented prehospital pain management likely reflects efforts toward complete documentation, as well as improved options for analgesia. Current combat casualty care documentation does not include any standardized pain scale.

Saving lives of wounded military warfighters often depends on the ability to resolve or mitigate the pathophysiology of hemorrhage, specifically diminished oxygen delivery to vital organs that leads to multiorgan failure and death. However, caring for hemorrhaging patients on the battlefield presents unique challenges that extend beyond applying a tourniquet and giving a blood transfusion, especially when battlefield care must be provided for a prolonged period. This review describes these challenges and potential strategies for treating hemorrhage on the battlefield in a prolonged casualty care situation.

Background The incidence of and mortality due to acute kidney injury is high in patients with traumatic shock. However, it is unclear how hemorrhage and trauma synergistically affect renal function, especially when timely volume resuscitation is not available. Method We hypothesized that trauma impairs renal tolerance to prolonged hemorrhagic hypotension. Sprague-Dawley rats were randomized into six groups: control, extremity trauma (ET), hemorrhage at 70 mm Hg (70-H), hemorrhage at 55 mm Hg (55-H), ET + 70 mm Hg (70-ETH), and ET + 55 mm Hg (55-ETH). Animals were anesthetized, and ET was induced via soft tissue injury and closed fibula fracture. Hemorrhage was performed via catheters 5 minutes after ET with target mean arterial pressure (MAP) clamped at 70 mm Hg or 55 mm Hg for up to 3 hours. Blood and urine samples were collected to analyze plasma creatinine (Cr), Cr clearance (CCr), renal oxygen delivery (DO2), urinary albumin, and kidney injury molecule-1 (KIM-1). Results Extremity trauma alone did not alter renal hemodynamics, DO2, or function. In 70-H, CCr was increased following hemorrhage, while Cr, renal vascular resistance (RVR), KIM-1, and albumin levels remained unchanged. Compared with 70-H, ET + 70 mm Hg exhibited increases in Cr and RVR with decreases in CCr and DO2. In addition, ET decreased the blood volume loss required to maintain MAP = 70 mm Hg by approximately 50%. Hemorrhage at 55 mm Hg and ET + 55 mm Hg exhibited a marked and similar decrease in CCr and increases in RVR, Cr, KIM-1, and albumin. However, ET greatly decreased the blood volume loss required to maintain MAP at 55 mm Hg and led to 50% mortality. Conclusion These results suggest that ET impairs renal and systemic tolerance to prolonged hemorrhagic hypotension. Thus, traumatic injury should be considered as a critical component of experimental studies investigating outcomes and treatment following hemorrhagic shock. Level of evidence This is an original article on basic science and does not require a level of evidence.

Background Military guidelines endorse early fasciotomy after revascularization of lower extremity injuries to prevent compartment syndrome, but the real-world impact is unknown. We assessed the association between fasciotomy and amputation and limb complications among lower extremitys with vascular injury. Methods A retrospectively collected lower extremity injury database was queried for limbs undergoing attempted salvage with vascular procedure (2004-2012). Limbs were categorized as having undergone fasciotomy or not. Injury and treatment characteristics were collected, as were intervention timing data when available. The primary outcome measure was amputation. Multivariate models examined the impact of fasciotomy on limb outcomes. Results Inclusion criteria were met by 515 limbs, 335 (65%) with fasciotomy (median 7.7 h postinjury). Of 212 limbs, 174 (84%) with timing data had fasciotomy within 30 min of initial surgery. Compartment syndrome and suspicion of elevated pressure was documented in 127 limbs (25%; 122 had fasciotomy). Tourniquet and shunt use, fracture, multiple arterial and combined arteriovenous injuries, popliteal involvement, and graft reconstruction were more common in fasciotomy limbs. Isolated venous injury and vascular ligation were more common in nonfasciotomy limbs. Fasciotomy timing was not associated with amputation. Controlling for limb injury severity, fasciotomy was not associated with amputation but was associated with limb infection, motor dysfunction, and contracture. Sixty-three percent of fasciotomies were open for >7 d, and 43% had multiple closure procedures. Fasciotomy revision (17%) was not associated with increased amputation or complications. Conclusions Fasciotomy after military lower extremity vascular injury is predominantly performed early, frequently without documented compartment pressure elevation. Early fasciotomy is generally performed in severely injured limbs with a subsequent high rate of limb complications.

Valproic acid (VPA) has been extensively used for treatment of anxiety and seizure. Recent studies have shown that VPA has cellular protective effects in preclinical models following severe hemorrhage. This study investigated the effects of VPA on coagulation and survival in pigs after traumatic hemorrhage and hypotensive resuscitation.Following baseline measurements, femur fracture was performed in 20 anesthetized and instrumented pigs (41 ± 2 kg), followed by hemorrhage of 55% of the estimated blood volume and a 10-minute shock period. Pigs were then resuscitated for 30 minutes with normal saline (NS) alone (NS group, n = 10, 4 mL/kg) or VPA solution (VPA group, n = 10, 90 mg/kg, 2 mL/kg of 45 mg VPA/mL, plus 2 mL NS/kg). All pigs were then monitored for 2 hours or until death. Hemodynamics were recorded, and blood samples were taken for blood and coagulation analysis (Rotem) at baseline, after hemorrhage, resuscitation, and 2 hours or death.Femur fracture and hemorrhage caused similar reductions in mean arterial pressure and cardiac output, and increase in heart rate in both groups. Resuscitation with NS or VPA did not return these measurements to baseline. No differences were observed in hematocrit, pH, lactate, base excess, or total protein between the groups. Compared with NS, resuscitation with VPA decreased platelet counts and prolonged activated partial thromboplastin time, with no differences in fibrinogen levels, prothrombin time, or any of the Rotem measurements between the two groups. Neither survival rates (NS, 7 of 10 pigs; VPA, 7 of 10 pigs) nor survival times after resuscitation (NS, 97 ± 40 minutes; VPA, 98 ± 43 minutes) differed between the groups.Following traumatic hemorrhage and hypotensive resuscitation in pigs, VPA provides no benefit toward improving coagulation function or survival times.

Peripheral vasoconstriction is the most critical compensating mechanism following hemorrhage to maintain blood pressure. On the battlefield, ketamine rather than opioids is recommended for pain management in case of hemorrhage, but effects of analgesics on compensatory vasoconstriction are not defined. We hypothesized that fentanyl impairs but ketamine preserves the peripheral vasoconstriction and blood pressure compensation following hemorrhage.Sprague-Dawley rats (11-13 weeks) were randomly assigned to control (saline vehicle), fentanyl, or ketamine-treated groups with or without hemorrhage (n = 8 or 9 for each group). Rats were anesthetized with Inactin (i.p. 10 mg/100 g), and the spinotrapezius muscles were prepared for microcirculatory observation. Arteriolar arcades were observed with a Nikon microscope, and vessel images and arteriolar diameters were recorded by using Nikon NIS Elements Imaging Software (Nikon Instruments Inc. NY). After baseline perimeters were recorded, the arterioles were topically challenged with saline, fentanyl, or ketamine at concentrations relevant to intravenous analgesic doses to determine direct vasoactive effects. After arteriolar diameters returned to baseline, 30% of total blood volume was removed in 25 minutes. Ten minutes after hemorrhage, rats were intravenously injected with an analgesic dose of fentanyl (0.6 μg/100 g), ketamine (0.3 mg/100 g), or a comparable volume of saline. For each drug or vehicle administration, the total volume injected was 0.1 mL/100 g. Blood pressure, heart rate, and arteriolar responses were monitored for 40 minutes.Topical fentanyl-induced vasodilation (17 ± 2%), but ketamine caused vasoconstriction (-15 ± 4%, p0.01). Following hemorrhage, intravenous ketamine did not affect blood pressure or respiratory rate, while fentanyl induced a slight and transient (5 minutes, p = 0.03 vs. saline group) decrease in blood pressure, with a profound and prolonged suppression in respiratory rate (10 minutes, with a peak inhibition of 57 ± 8% of baseline, p0.01). The compensatory vasoconstriction observed after hemorrhage was not affected by ketamine treatment. However, after fentanyl injection, although changes in blood pressure were transiently present, arteriolar constriction to hemorrhage was absent and replaced with a sustained vasodilation (78 ± 25% to 36 ± 22% of baseline during the 40 minutes after injection, p0.01).Ketamine affects neither systemic nor microcirculatory compensatory responses to hemorrhage, providing preclinical evidence that ketamine may help attenuate adverse physiological consequences associated with opioids following traumatic hemorrhage. Microcirculatory responses are more sensitive than systemic response for evaluation of hemodynamic stability during procedures associated with pain management.

IntroductionAirway compromise is the second leading cause of potentially survivable death on the battlefield. The purpose of this study was to better understand wartime prehospital airway patients.Materials and MethodsThe Role 2 Database (R2D) was retrospectively reviewed for adult patients injured in Afghanistan between February 2008 and September 2014. Of primary interest were prehospital airway interventions and mortality. Prehospital combat mortality index (CMI-PH), hemodynamic interventions, injury mechanism, and demographic data were also included in various statistical analyses.ResultsA total of 12,780 trauma patients were recorded in the R2D of whom 890 (7.0%) received prehospital airway intervention. Airway intervention was more common in patients who ultimately died (25.3% vs. 5.6%); however, no statistical association was found in a multivariable logistic regression model (OR 1.28, 95% CI 0.98–1.68). Compared with U.S. military personnel, other military patients were more likely to receive airway intervention after adjusting for CMI-PH (OR 1.33, 95% CI 1.07–1.64).ConclusionsIn the R2D, airway intervention was associated with increased odds of mortality, although this was not statistically significant. Other patients had higher odds of undergoing an airway intervention than U.S. military. Awareness of these findings will facilitate training and equipment for future management of prehospital/prolonged field care airway interventions.

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.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.Hemorrhage resulted in mild hypotension. Minimal resuscitation was required during the hypotensive phase, and survival rate was 100%. Significant increases (p0.001) in alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, and lactate dehydrogenase occurred on Day 1 after PH, and were significantly greater (p0.001) 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 (p0.10).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.Basic science research, Level of evidence not required for basic science research.

Acute compartment syndrome (ACS) is a serious medical condition that can occur following traumatic injury to an extremity. If left undiagnosed, ACS can eventuate in amputation of the limb or even death. Because of this, fasciotomy to release the pressure within the muscle and restore tissue perfusion is often performed upon suspicion of ACS, as the sequelae to fasciotomy are less severe than those associated with not performing the fasciotomy. Currently, the "gold standard" of diagnosis is based on clinical assessment of such symptoms as pain out of proportion to the injury, obvious high pressure and swelling, pain on passive stretch of the muscles in the affected compartment, and deficits in sensory and/ormotor functions. Diagnosis is often confirmed using invasive measurements of intramuscular pressure (IMP); however, controversy exists as to how direct IMP measurement should be accomplished and threshold pressures for accurate diagnosis. Because of this and the attendant issues with invasive measurements, investigators have been searching over the last 25 years for a noninvasive means to quantitatively measure IMP or perfusion to the limb. The purpose of this review is to summarize the current state of the art of noninvasive devices that could potentially be used to diagnose ACS accurately and objectively. To do this, we divide the discussion into those medical devices that primarily measure mechanical surrogates of IMP (e.g., tissue hardness or myofascial displacement) and those that primarily measure indices of tissue perfusion (e.g., tissue oxygen saturation via near-infraredspectroscopy). While near-infrared spectroscopy-basedtechnologies have shown the most promise, whether such technologies will be of diagnostic benefit await the completion of ongoing clinical trials. LEVEL OF EVIDENCE: Systematic Review, level II.

The incidence of and mortality due to acute kidney injury is high in patients with traumatic shock. However, it is unclear how hemorrhage and trauma synergistically affect renal function, especially when timely volume resuscitation is not available.We hypothesized that trauma impairs renal tolerance to prolonged hemorrhagic hypotension. Sprague-Dawley rats were randomized into six groups: control, extremity trauma (ET), hemorrhage at 70 mm Hg (70-H), hemorrhage at 55 mm Hg (55-H), ET + 70 mm Hg (70-ETH), and ET + 55 mm Hg (55-ETH). Animals were anesthetized, and ET was induced via soft tissue injury and closed fibula fracture. Hemorrhage was performed via catheters 5 minutes after ET with target mean arterial pressure (MAP) clamped at 70 mm Hg or 55 mm Hg for up to 3 hours. Blood and urine samples were collected to analyze plasma creatinine (Cr), Cr clearance (CCr), renal oxygen delivery (DO2), urinary albumin, and kidney injury molecule-1 (KIM-1).Extremity trauma alone did not alter renal hemodynamics, DO2, or function. In 70-H, CCr was increased following hemorrhage, while Cr, renal vascular resistance (RVR), KIM-1, and albumin levels remained unchanged. Compared with 70-H, ET + 70 mm Hg exhibited increases in Cr and RVR with decreases in CCr and DO2. In addition, ET decreased the blood volume loss required to maintain MAP = 70 mm Hg by approximately 50%. Hemorrhage at 55 mm Hg and ET + 55 mm Hg exhibited a marked and similar decrease in CCr and increases in RVR, Cr, KIM-1, and albumin. However, ET greatly decreased the blood volume loss required to maintain MAP at 55 mm Hg and led to 50% mortality.These results suggest that ET impairs renal and systemic tolerance to prolonged hemorrhagic hypotension. Thus, traumatic injury should be considered as a critical component of experimental studies investigating outcomes and treatment following hemorrhagic shock.This is an original article on basic science and does not require a level of evidence.

Ketamine is the recommended analgesic on the battlefield for soldiers with hemorrhage, despite a lack of supportive evidence from laboratory or clinical studies. Hence, this study determined the effects of ketamine analgesia on cardiorespiratory responses and survival to moderate (37% blood volume; n = 8/group) or severe hemorrhage (50% blood volume; n = 10/group) after trauma in rats. We used a conscious hemorrhage model with extremity trauma (fibular fracture + soft tissue injury) while measuring mean arterial pressure (MAP), heart rate (HR), and body temperature (Tb) by telemetry, and respiration rate (RR), minute volume (MV), and tidal volume (TV) via whole body plethysmography. Male rats received saline (S) or 5.0 mg/kg ketamine (K) (100 µL/100 g body wt) intra-arterially after trauma and hemorrhage. All rats survived 37% hemorrhage. For 50% hemorrhage, neither survival times [180 min (SD 78) vs. 209 min (SD 66)] nor percent survival (60% vs. 80%) differed between S- and K-treated rats. After 37% hemorrhage, K (compared with S) increased MAP and decreased Tb and MV. After 50% hemorrhage, K (compared with S) increased MAP but decreased HR and MV. K effects on cardiorespiratory function were time dependent, significant but modest, and transient at the analgesic dose given. K effects on Tb were also significant but modest and more prolonged. With the use of this rat model, our data support the use of K as an analgesic in injured, hypovolemic patients.NEW & NOTEWORTHY Ketamine administration at a dose shown to alleviate pain in nonhemorrhaged rats with extremity trauma had only modest and transient effects on multiple aspects of cardiorespiratory function after both moderate (37%) and severe (50%) traumatic hemorrhages. Such effects did not alter survival.

Appropriate airway management is essential in trauma and critically ill patients. Prolonged mechanical ventilation can result in overventilation-induced lung barotrauma, but few studies have examined the consequence of acute overventilation. We investigated the outcome of hemorrhage followed by 1 h of overventilation in swine. We found that acute overventilation, as could be seen in the prehospital phase of trauma care, does not produce evidence of adverse effects on otherwise healthy lungs following moderate hemorrhage.

Endotracheal intubation is a common life-saving procedure implemented in emergency care to ensure patient oxygenation, but it is difficult and often performed in suboptimal conditions leading to high rates of patient complications. Undetected misplacement in the esophagus is a preventable complication that can lead to fatalities in 5–10% of patients who undergo emergency intubation. End-tidal carbon dioxide monitoring and other proper placement detection methods are useful, yet the problem of misplacement persists. Our previous work demonstrated the utility of spectral reflectance sensors for differentiating esophageal and tracheal tissues, which can be used to confirm proper endotracheal tube placement. In this study, we examine the effectiveness of spectral characterization in the presence of saline, blood, “vomit”, and soot in the trachea. Our results show that spectral properties of the trachea that differentiate it from the esophagus persist in the presence of these substances. This work further confirms the potential usefulness of this novel detection technology in field applications.

Airway simulators, or training manikins, are frequently used in research studies for device development and training purposes. This study was designed to determine the anatomic accuracy of the most frequently used low-fidelity airway training manikins. Computerised tomography scans and ruler measurements were taken of the SynDaver® , Laerdal® and AirSim® manikins. These measurements were compared with human computerised tomography (CT) scans (n = 33) from patients at the University of Michigan Medical Center or previously published values. Manikin measurements were scored as a percentile among the distribution of the same measurements in the human population and 10 out of 27 manikin measurements (nine measurements each in three manikins) were outside of two standard deviations from the mean in the participants. All three manikins were visually identifiable as outliers when plotting the first two dimensions from multidimensional scaling. In particular, the airway space between the epiglottis and posterior pharyngeal wall, through which airway devices must pass, was too large in all three manikins. SynDaver, Laerdal and AirSim manikins do not have anatomically correct static dimensions in relation to humans and these inaccuracies may lead to imprecise airway device development, negatively affect training and cause over-confidence in users.

Proper placement of the tracheal tube requires confirmation, and the predominant method in addition to clinical signs is the presence of end-tidal carbon dioxide. Such is the importance of confirmation that novel methods may also have a place. We previously demonstrated using ex-vivo swine tissue a unique spectral reflectance characteristic of tracheal tissue that differs from oesophageal tissue. We hypothesised that this characteristic would be present in living swine tissue and human cadavers. Reflectance spectra in the range 500-650 nm were captured using a customised fibreoptic probe, compact spectrometer and white light source from both the trachea and the oesophagus in anesthetised living swine and in human cadavers. A tracheal detection algorithm using ratio comparisons of reflectance was developed. The existence of the unique tracheal characteristic in both in-vivo swine and cadaver models was confirmed (p < 0.0001 for all comparisons between tracheal and oesophageal tissue at all target wavelengths in both species). Furthermore, our proposed tracheal detection algorithm exhibited a 100% positive predictive value in both models. This has potential utility for incorporation into airway management devices.

Lower body negative pressure (LBNP) simulates hemorrhage in human subjects. Most subjects (67%) exhibited high tolerance (HT) to hypovolemia, while the remainder (33%) had low tolerance (LT). To investigate the mechanisms for decompensation to central hypovolemia in HT and LT subjects, we characterized the time course of total peripheral resistance (TPR), heart rate (HR), and muscle sympathetic nerve activity (MSNA) during LBNP to tolerance determined by the onset of decompensation (presyncope, PS). We hypothesized that 1) maximum (Max) TPR, HR, and MSNA would coincide, and 2) PS would result from simultaneous decreases in TPR, HR, and MSNA in LT and HT subjects but occur earlier in LT than in HT subjects. Max TPR was lower and occurred earlier in LT ( n = 59) than in HT ( n = 113) subjects (LT: 24 ± 1 mmHg·min·1−1at 756 ± 31 s; HT: 28 ± 1 mmHg·min·1−1at 1,265 ± 37 s, P < 0.01). Max TPR occurred several minutes before PS. During subsequent decrease in TPR, HR and MSNA continued to increase. Max HR (LT: 111 ± 2 beat/min at 923 ± 27 s; HT: 130 ± 2 beats/min at 1489 ± 23 s, P < 0.01) occurred several seconds before PS. Higher MSNA ( P < 0.01) was attained in HT ( n = 10; 51 ± 5 bursts/min at max TPR; 54 ± 5 bursts/min at max HR) than LT subjects ( n = 4; 41 ± 8 bursts/min at max TPR; 39 ± 8 bursts/min at max HR). The onset of cardiovascular decompensation is a biphasic process in which vasodilation occurs before bradycardia and sympathetic withdrawal. This pattern was similar in LT and HT but occurred earlier in LT subjects. We conclude that sudden bradycardia plays a critical role in the determination of tolerance to central hypovolemia.

Airway management is of critical importance in combat trauma patients. Airway compromise is the second leading cause of potentially survivable death on the battlefield and accounts for approximately 1 in 10 preventable deaths. Reports from the Iraq and Afghanistan wars indicate 4% to 7% incidence of airway interventions on casualties transported to combat hospitals. The goal of this study was to describe airway management in the prehospital combat setting and document airway devices used on the battlefield.This study is a retrospective review of casualties that required a prehospital lifesaving airway intervention during combat operations in Afghanistan. We obtained data from the Prehospital Trauma Registry that was linked to the Department of Defense Trauma Registry for outcome data for the time period between January 2013 and September 2014.Seven hundred five total trauma patients were included, 16.9% required a prehospital airway management procedure. There were 132 total airway procedures performed, including 83 (63.4%) endotracheal intubations and 26 (19.8%) nasopharyngeal airway placements. Combat medics were involved in 48 (36.4%) of airway cases and medical officers in 73 (55.3%). Most (94.2%) patients underwent airway procedures due to battle injuries caused by explosion or gunshot wounds. Casualties requiring airway management were more severely injured and less likely to survive as indicated by Injury Severity Score, responsiveness level, Glascow Coma Scale, and outcome.Percentages of airway interventions more than tripled from previous reports from the wars in Afghanistan and Iraq. These changes are significant, and further study is needed to determine the causes. Casualties requiring airway interventions sustained more severe injuries and experienced lower survival than patients who did not undergo an airway procedure, findings suggested in previous reports.Prognostic and epidemiological study, level III.

Walter B. Cannon (1871–1945), perhaps America’s preeminent physiologist, volunteered for service with the Army Expeditionary Force (AEF) during World War I. He initially served with Base Hospital No. 5, a unit made up of Harvard clinicians, before moving forward to the front lines to serve at a casualty clearing station run by the British. During his time there, he performed research on wounded soldiers to understand the nature and causes of traumatic shock. Subsequently, Cannon performed animal experimentation on the causes of traumatic shock in the London laboratory of Dr. William Bayliss before being assigned to the AEF Central Medical Laboratory in Dijon, France, where he continued his experimental studies. During this time, he also developed and taught a curriculum on resuscitation of wounded soldiers to medical providers. Although primarily a researcher and teacher, Cannon also performed clinical duties throughout the war, serving with distinction under fire. After the war, Cannon wrote a monograph entitled Traumatic Shock (New York: Appleton, 1923), which encapsulated the knowledge that had been gained during the war, both from direct observation of wounded soldiers, as well as laboratory experimentation on the causes and treatment of traumatic shock. In his monograph, Cannon elucidates a number of principles concerning hemorrhagic shock that were later forgotten, only to be “rediscovered” during the current conflicts in Iraq and Afghanistan. This paper summarizes Cannon’s wartime experiences and the knowledge gained concerning traumatic shock during World War I, with a comparison of current combat casualty care practices and knowledge to that which Cannon and his colleagues understood a century ago.

Loss of a patent airway is a significant cause of prehospital death. Endotracheal intubation is the gold standard of care but has a high rate of failure and complications, making development of new devices vital. We previously showed that tracheal tissue has a unique spectral profile which could be utilized to confirm correct airway device placement. Therefore, the goals of this study were twofold: 1‐ to develop an airway obstruction model and 2‐ use that model to assess how airway compromise affects tissue reflectance. Female swine were anesthetized, intubated, and instrumented. Pigs were allowed to breathe spontaneously and underwent either slow‐ or rapid‐onset obstruction until a real‐time pulse oximeter reading of ≤50%. At baseline, 25%, 50%, 75%, and 100% obstruction, a fiber‐optic reflection probe was inserted into the trachea and esophagus to capture reflectance spectra. Both slow‐ and rapid‐onset obstruction significantly decreased arterial oxygen concentration (sO2) and increased partial pressure of CO2 (pCO2). The presence of the tracheal‐defining spectral profile was confirmed and remained consistent despite changes in sO2 and pCO2. This study validated a model of slow‐ and rapid‐airway obstruction that results in significant hypoxia and hypercapnia. This is valuable for future testing of airway device components that may improve airway management. Additionally, our data support the ability of spectral reflectance to differentiate between tracheal and esophageal tissues in the presence of a clinical condition that decreases oxygen saturation.

Toxoplasma gondii (T. gondii) IgG seropositivity and serointensity have been previously associated with suicidal self-directed violence (SSDV). Although associations with unipolar depression have also been investigated, the results have been inconsistent, possibly as a consequence of high heterogeneity. We have now studied this association in a more homogeneous population, [that is (i.e.) Old Order Amish (OOA)] with previously reported high T. gondii seroprevalence. In 306 OOA with a mean age of 46.1 ± 16.7 years, including 191 (62.4%) women in the Amish Wellness Study, we obtained both T. gondii IgG titers (by enzyme-linked immunosorbent assay [ELISA]), and depression screening questionnaires (Patient Health Questionnaire [PHQ-9] [n = 280] and PHQ-2 [n = 26]). Associations between T. gondii IgG and dysphoria/hopelessness and anhedonia scores on depression screening questionnaires were analyzed using multivariable linear methods with adjustment for age and sex. Serointensity was associated with both current dysphoria/hopelessness (p = 0.045) and current combined anhedonia and dysphoria/hopelessness (p = 0.043), while associations with simple anhedonia and past/lifelong (rather than current) phenotypes were not significant. These results indicate the need for larger longitudinal studies to corroborate the association between dysphoria/hopelessness and T. gondii IgG-titers. Current hopelessness is a known risk factor for SSDV which responds particularly well to cognitive behavioral therapy, and may be a focused treatment target for T. gondii-positive individuals at high-risk for SSDV.

Background Pain management is important in prehospital care of patients with extremity trauma (ET). The goal of this study was to establish a rat model of ET for prehospital pain research and validate it using pain behaviors and analgesics. Methods Rats were anesthetized using isoflurane, and ET was induced in one hindlimb via clamping retrofemoral tissues for 30 seconds, followed by closed fibula fracture. Rats regained consciousness after ET. Pain responses in the injured hindlimb to thermal hyperalgesia (paw withdrawal latency [PWL]), mechanical allodynia (paw withdrawal pressure [PWP]), and weight bearing (WB) were determined before and 90 minutes after ET. Morphine (2 mg/kg), fentanyl (10 μg/kg), sufentanil (1 μg/kg), ketamine (5 mg/kg), or vehicle (saline) were then administered via intravenous (i.v.) injection, followed by PWL, PWP, and WB assessments at 10 minutes, 40 minutes, 80 minutes, and 120 minutes after analgesia. Results After ET, PWL, PWP, and WB were significantly decreased by 61 ± 4%, 64 ± 8%, and 65 ± 4%, respectively, compared with pre-ET values. These pain behaviors were maintained for 3 hours to 4 hours. Compared with the saline group, opioid analgesics significantly increased PWL for at least 80 minutes, with sufentanil exhibiting the highest analgesic effect. An increase in PWL was only observed at 10 minutes after ketamine. The PWP was transiently increased with opioid analgesics for 10 minutes to 40 minutes, but was not changed with ketamine. Weight bearing was improved with opioid analgesics for at least 2 hours, but only for up to 80 minutes with ketamine. Conclusion Our ET model includes long bone fracture and soft tissue injury, but no fixation surgery, mimicking prehospital ET. Our model produces acute, steady, and reproducible trauma-related pain behaviors, and is clinically relevant regarding the pain behaviors and established responses to common analgesics. This model of acute pain due to ET is ideal for prehospital pain management research.

Early efforts in physiological research in the United States were produced by lone investigators working in laboratories funded by their own medical practices. In Europe, however, Claude Bernard and Carl Ludwig produced a new model of scientific research laboratories funded by the state that sought to develop the pursuit of biomedical research as an occupation. American physicians such as Henry Pickering Bowditch and S. Weir Mitchell were exposed to this new “research ethic” during their international studies and brought this new perspective home to America. Along with H. Newell Martin, these men began training professional physiologists who would assume new research positions in academic institutions. In 1887, Bowditch, Mitchell, and H. Newell Martin proposed the formation of a new society for these professional physiologists, the American Physiological Society (APS). Seventeen of the original twenty-eight members met on December 30, 1887, in New York City, NY, to establish APS. From these humble beginnings, APS evolved to become a force for change in American biomedical science.

BACKGROUND: Hemorrhage is a major cause of soldier death; it must be quickly identified and appropriately treated. We developed a prototype patient monitor that noninvasively and continuously determines muscle oxygen saturation (SmO2), muscle pH (pHm), and a regional assessment of blood volume (HbT) using near-infrared spectroscopy. Previous demonstration in a model of progressive, central hypovolemia induced by lower body negative pressure (LBNP) showed that SmO2 provided an early indication of impending hemodynamic instability in humans. In this review, we expand the number of subjects and provide an overview of the relationship between the muscle and sublingual microcirculation in this model of compensated shock. METHODS: Healthy human volunteers (n 30) underwent progressive LBNP in 5-minute intervals. Standard vital signs, along with stroke volume (SV), total peripheral resistance, functional capillary density, SmO2, HbT, and pHm were measured continuously throughout the study. RESULTS AND DISCUSSION: SmO2 and SV significantly decreased during the first level of central hypovolemia ( 15 mm Hg LBNP), whereas vital signs were later indicators of impending cardiovascular collapse. SmO2 declined with SV and inversely with total peripheral resistance throughout LBNP. HbT was correlated with declining functional capillary density, suggesting vasoconstriction as a cause for decreased SmO2 and subsequently decreased pHm. CLINICAL TRANSLATION: The monitor has been miniaturized to a 58-g solid-state sensor that is currently being evaluated on patients with dengue hemorrhagic fever. Early results demonstrate significant decreases in SmO2 similar to those observed with progressive reductions in central blood volume. As such, this technology has the potential to (1) provide a monitoring capability for both nontraumatic and traumatic hemorrhage and (2) help combat medics triage casualties and monitor patients during lengthy transport from combat areas.

Early detection and management of shock are important in optimizing clinical outcomes. One regional marker, sublingual capnography (SLCO2), is particularly appealing as redistribution of blood flow away from the sublingual mucosa can happen very early in the compensatory phase of hypovolemic shock. Our objective was to test the hypothesis that SLCO2 would detect early hypovolemia in a human laboratory model of hemorrhage: progressive lower body negative pressure until onset of cardiovascular collapse. Eighteen healthy nonsmoking subjects (10 males, 8 females) with mean age of 28 (SD, 8) years, body weight of 72 (SD, 13) kg, and height of 172 (SD, 9) cm were recruited to participate, of whom 17 completed the experiment. Average time to presyncope was 1,579 +/- 72 s (mean +/- SE). At the time of cardiovascular collapse, lower body negative pressure altered (P 0.001) systolic blood pressure (mean +/- SE: 130 +/- 3 vs. 98 +/- 2 mm Hg), pulse pressure (mean +/- SE: 58 +/- 2 vs. 33 +/- 2 mm Hg), and heart rate (mean +/- SE: 63 +/- 3 vs. 102 +/- 6 beats/min) when compared with baseline, whereas SLCO2 did not change (49.1 +/- 1.0 vs. 48.6 +/- 1.5 mm Hg, P 0.624). In a model of progressive central hypovolemia in humans, we did not detect metabolic derangements in the sublingual mucosa as measured by SLCO2.

Muscle oxygen saturation (SmO2) is a very early indicator of internal bleeding, but reaches a low and constant value when organ oxygen utilisation is at a maximum. With haemorrhage, muscle pH (pHm) continues to decline indicating the severity of injury. During resuscitation, it is important to continue treatment until acidosis is reversed, even after normal levels of tissue oxygen are restored. SmO2 and pHm can be determined continuously and non-invasively using near infrared (NIR) spectroscopy. Simultaneous determination of SmO2 and pHm from the same spectra are required for continuous monitoring of trauma patients. Acidosis enhances the release of oxygen from haemoglobin when there is insufficient oxygen available to the tissue (Bohr effect). An NIR spectroscopic-based patient monitor, however, must be capable of detecting independent variations in both pHm and SmO2. The results from an in vitro study of whole blood demonstrate spectral changes at the isosbestic point (800 nm) which were a strong function of pH, but independent of blood SO2 and scattering (cell size), suggesting that hydrogen ions directly affect the NIR spectrum in the region between 700 nm and 900 nm. Using a dual source, fibre optic-based system, NIR spectra (725–880 nm) were also collected from 40 human subjects undergoing lower body negative pressure as an experimental model of haemorrhage. SmO2 and pHm were calculated from the spectra collected from the forearm of each subject. Every muscle absorbance spectrum was fitted to a Taylor expansion attenuation model based upon Beer's law modified for a scattering component to calculate SmO2. The same spectra were corrected for subject variability using previously determined coefficients for principal component analysis loading correction. The corrected spectra were then used in a partial least-squares regression model previously developed from exercising subjects. pHm and SmO2 determined from the same spectra followed different time courses during simulated haemorrhage on human subjects. Taken together, results from these in vitro and in vivo studies show that the NIR spectroscopic-based monitor simultaneously and independently assesses SmO2 and pHm.

The editors of Advances in Physiology Education and the leadership of the American Physiological Society (APS) History of Physiology Group would like to express their profound appreciation to Charles M. Tipton, PhD, for his extraordinary service to both the journal and to the History of Physiology

Hemorrhage is accompanied by baroreflex-mediated tachycardia and vasoconstriction. The difference between baseline and maximum responses is defined as the heart rate (HR) and vasoconstrictor ‘reserve’. To test the hypothesis that higher HR and vasoconstrictor reserves in subjects with high tolerance (HT) to central hypovolemia is associated with greater reserve for sympathoexcitation and vagal withdrawal compared with low tolerant (LT) subjects. R–R intervals (RRI), systolic arterial pressure (SAP), estimated stroke volume, and muscle sympathetic nerve activity (MSNA) were measured during lower body negative pressure (LBNP) designed to induce pre-syncope. Subjects with tolerance ≤60 mmHg LBNP were classified as LT (n = 22) while subjects who tolerated LBNP levels >60 mmHg were classified as HT (n = 56). Spontaneous cardiac baroreflex sensitivity (BRS) was assessed via RRI-SAP down–down sequences. HR reserve in HT subjects (+52 ± 2 bpm) was twofold greater (P

The spectral power of low frequency oscillations of systolic arterial pressure (SAP(LF)) has been used as a non-invasive surrogate of muscle sympathetic nerve activity (MSNA) in both experimental and clinical situations. For SAP(LF) to be used in this way, a relationship must exist between SAP(LF) and MSNA within individuals during sympathetic activation. Using progressive central hypovolaemia to induce sympathetic activation, we hypothesised that SAP(LF) would correlate with MSNA in all subjects. ECG, beat-by-beat arterial pressure and MSNA were recorded in humans (n = 20) during a progressive lower body negative pressure (LBNP) protocol designed to cause presyncope in all subjects. Arterial pressure oscillations were assessed in the low frequency (LF; 0.04-0.15 Hz) domain using a Fourier transform. For the entire group, SAP(LF), MSNA burst frequency, and total MSNA increased during LBNP. Values for coefficients of determination (r(2)) describing the linear associations of SAP(LF) with MSNA burst frequency and total MSNA were 0.73 and 0.84, but rose to 0.89 and 0.98 when curvilinear fits were used, indicating that the relationship is curvilinear rather than linear. Associations between SAP(LF) and MSNA within each individual subject, however, varied widely for both MSNA burst frequency and total MSNA, whether derived by linear (r(2) range, 1.7 × 10(-6) to 0.99) or polynomial (r(2) range, 0.09 to 1.0) regression analysis. Similar results were obtained when relationships between low frequency oscillations in diastolic arterial pressure and MSNA were evaluated. These results do not support the use of low frequency oscillations in arterial pressure as a non-invasive measure of sympathetic outflow for individual subjects during sympathetic activation.