Blood volume and hemodynamics during treatment of major hemorrhage with Ringer solution, 5% albumin, and 20% albumin: a single-center randomized controlled trial.

BACKGROUND: Volume replacement with crystalloid fluid is the conventional treatment of hemorrhage. We challenged whether a standardized amount of 5% or 20% albumin could be a viable option to maintain the blood volume during surgery associated with major hemorrhage. Therefore, the aim of this study was to quantify and compare the plasma volume expansion properties of 5% albumin, 20% albumin, and Ringer-lactate, when infused during major surgery. METHODS: In this single-center randomized controlled trial, fluid replacement therapy to combat hypovolemia during the hemorrhagic phase of cystectomy was randomly allocated in 42 patients to receive either 5% albumin (12 mL/kg) or 20% albumin (3 mL/kg) over 30 min at the beginning of the hemorrhagic phase, both completed by a Ringer-lactate replacing blood loss in a 1:1 ratio, or Ringer-lactate alone to replace blood loss in a 3:1 ratio. Measurements of blood hemoglobin over 5 h were used to estimate the effectiveness of each fluid to expand the blood volume using the following regression equation: blood loss plus blood volume expansion = factor + volume of infused albumin + volume of infused Ringer-lactate. RESULTS: The median hemorrhage was 848 mL [IQR: 615-1145]. The regression equation showed that the Ringer-lactate solution expanded the plasma volume by 0.18 times the infused volume while the corresponding power of 5% and 20% albumin was 0.74 and 2.09, respectively. The Ringer-lactate only fluid program resulted in slight hypovolemia (mean, - 313 mL). The 5% and 20% albumin programs were more effective in filling the vascular system; this was evidenced by blood volume changes of only + 63 mL and - 44 mL, respectively, by long-lasting plasma volume expansion with median half time of 5.5 h and 4.8 h, respectively, and by an increase in the central venous pressure. CONCLUSION: The power to expand the plasma volume was 4 and almost 12 times greater for 5% albumin and 20% albumin than for Ringer-lactate, and the effect was sustained over 5 h. The clinical efficacy of albumin during major hemorrhage was quite similar to previous studies with no hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov NCT05391607, date of registration May 26, 2022.

Predicting fluid responsiveness in spontaneously breathing parturients undergoing caesarean section via carotid artery blood flow and velocity time integral measured by carotid ultrasound: a prospective cohort study.

BACKGROUND: Present evidence suggests that the Doppler ultrasonographic indices, such as carotid artery blood flow (CABF) and velocity time integral (VTI), had the ability to predict fluid responsiveness in non-obstetric patients. The purpose of this study was to assess their capacity to predict fluid responsiveness in spontaneous breathing parturients undergoing caesarean section and to determine the effect of detecting and management of hypovolemia (fluid responsiveness) on the incidence of hypotension after anaesthesia. METHODS: A total of 72 full term singleton parturients undergoing elective caesarean section were enrolled in this study. CABF, VTI, and hemodynamic parameters were recorded before and after fluid challenge and assessed by carotid artery ultrasonography. Fluid responsiveness was defined as an increase in stroke volume index (SVI) of 15% or more after the fluid challenge. RESULTS: Thirty-one (43%) patients were fluid responders. The area under the ROC curve to predict fluid responsiveness for CABF and VTI were 0.803 (95% CI, 0.701-0.905) and 0.821 (95% CI, 0.720-0.922). The optimal cut-off values of CABF and VTI for fluid responsiveness was 175.9 ml/min (sensitivity of 74.0%; specificity of 78.0%) and 8.7 cm/s (sensitivity of 67.0%; specificity of 90.0%). The grey zone for CABF and VTI were 114.2-175.9 ml/min and 6.8-8.7 cm/s. The incidence of hypotension after the combined spinal-epidural anaesthesia (CSEA) was significantly higher in the Responders group 25.8% (8/31) than in the Non-Responders group 17.1(7/41) (P < 0.001). The total incidence of hypotension after CSEA of the two groups was 20.8% (15/72). CONCLUSIONS: Ultrasound evaluation of CABF and VTI seem to be the feasible parameters to predict fluid responsiveness in parturients undergoing elective caesarean section and detecting and management of hypovolemia (fluid responsiveness) could significantly decrease incidence of hypotension after anaesthesia. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry (ChiCTR) ( www.chictr.org ), registration number was ChiCTR1900022327 (The website link: https://www.chictr.org.cn/showproj.html?proj=37271 ) and the date of trial registration was in April 5, 2019. This study was performed in accordance with the Declaration of Helsinki and approved by the Research Ethics Committee of Women's Hospital, Zhejiang University School of Medicine (20,180,120).

Maldistribution of fluid in preeclampsia: a secondary kinetic analysis.

BACKGROUND: Hypovolemia and peripheral edema are frequent components of preeclampsia. The level of the dysregulation of the body fluid distribution is unclear, which complicates the choice of infusion fluid during surgery. The present fluid kinetic study challenges whether the maldistribution of fluid is due to increased capillary leakage or to poor return of already distributed fluid, which occurs via lymphatic pathways. METHODS: Ringers solution was infused in 10 awake non-pregnant women, eight healthy pregnant women, and in eight women with mild-to-moderately severe preeclampsia. Distribution and redistribution of the infused fluid was calculated with mixed models kinetics based on the excreted urine volumes and 675 measurements of hemodilution. Differences in fluid kinetics between the three groups were studied with covariance analysis. RESULTS: The return flow of fluid volume to the plasma after distribution (rate parameter k21) was almost zero in women with preeclampsia, while the rate was normal in the other two groups (P< 0.001). By contrast, the capillary leakage rate of fluid in response to the infusion (k12) was normal. The urinary excretion (k10) was moderately accelerated. CONCLUSION: Decreased flow of extravascular fluid to the plasma was the key disturbance in women with preeclampsia. Such decreased flow alone promotes hypovolemia, peripheral edema, and hypoalbuminemia, and may be explained by inhibition of lymphatic pumping and/or a decreased interstitial hydrostatic pressure due to the presence of vasoactive and inflammatory signal molecules. The moderately accelerated urine flow may be due to "pressure diuresis" in response to hypertension.

Incidence and risk factors of acute kidney injury in patients with malignant tumors: a systematic review and meta-analysis.

BACKGROUND: There are significant differences in the incidence and risk factors of tumor patients, and there is no relevant statistical data. Therefore, this study aims to clarify the incidence and risk factors of acute kidney injury (AKI) in malignant tumor patients and compare critically ill patients with non-critically ill patients. METHODS: Relevant literature on the occurrence of AKI in malignant tumors was retrieved from databases. Two authors independently screened and evaluated the eligibility and quality of the literature and extracted the data. The Stata 12.0 software was used for meta-analysis. RESULTS: A total of 3922 articles were initially retrieved, and 24 articles were finally included, 8 of which were about critically ill malignant tumor patients, and 16 were about malignant tumor patients. Among the 4107 patients included in the 8 studies on critically ill malignant tumors, 1932 developed AKI, with an incidence rate of 52% (95%CI 34-70%, I2 = 99%). The risk factors for AKI in critically ill malignant tumor patients were sepsis and hypovolemia, which were different from those in non-critically ill patients. Among the 292,874 patients included in the 16 studies on malignant tumors, 51,211 developed AKI, and the combined incidence rate was 24% (95%CI 17-30%, I2 = 100%). The risk factors for AKI in critical malignant tumor patients were sepsis and hypovolemia. CONCLUSION: This meta-analysis shows that the incidence of AKI in critically ill malignant tumor patients is consistent with that in other critically ill patients, and independent risk factors are sepsis and hypovolemia. The incidence of AKI in malignant tumor patients is higher than that in other patients, and tumor is a risk factor for AKI. This study has been registered in INPLASY (INPLASY202320079),Registered February 18,2023.

Superiority of compensatory reserve measurement compared with the Shock index for early and accurate detection of reduced central blood volume status.

BACKGROUND: Shock index (SI) equals the ratio of heart rate (HR) to systolic blood pressure (SBP) with clinical evidence that it is more sensitive for trauma patient status assessment and prediction of outcome compared with either HR or SBP alone. We used lower body negative pressure (LBNP) as a human model of central hypovolemia and compensatory reserve measurement (CRM) validated for accurate tracking of reduced central blood volume to test the hypotheses that SI: (1) presents a late signal of central blood volume status; (2) displays poor sensitivity and specificity for predicting the onset of hemodynamic decompensation; and (3) cannot identify individuals at greatest risk for the onset of circulatory shock. METHODS: We measured HR, SBP, and CRM in 172 human subjects (19-55 years) during progressive LBNP designed to determine tolerance to central hypovolemia as a model of hemorrhage. Subjects were subsequently divided into those with high tolerance (HT) (n = 118) and low tolerance (LT) (n = 54) based on completion of 60 mm Hg LBNP. The time course relationship between SI and CRM was determined and receiver operating characteristic (ROC) area under the curve (AUC) was calculated for sensitivity and specificity of CRM and SI to predict hemodynamic decompensation using clinically defined thresholds of 40% for CRM and 0.9 for SI. RESULTS: The time and level of LBNP required to reach a SI = 0.9 (~60 mm Hg LBNP) was significantly greater ( p < 0.001) compared with CRM that reached 40% at ~40 mm Hg LBNP. Shock index did not differ between HT and LT subjects at 45 mm Hg LBNP levels. ROC AUC for CRM was 0.95 (95% CI = 0.94-0.97) compared with 0.91 (0.89-0.94) for SI ( p = 0.0002). CONCLUSION: Despite high sensitivity and specificity, SI delays time to detect reductions in central blood volume with failure to distinguish individuals with varying tolerances to central hypovolemia. LEVEL OF EVIDENCE: Diagnostic Test or Criteria; Level III.

A case of septic shock due to delayed diagnosis of Cryptosporidium infection after liver transplantation.

BACKGROUND: Cryptosporidium is recognized as a significant pathogen of diarrhea disease in immunocompromised hosts, and studies have shown that Cryptosporidium infection is high in solid organ transplantation (SOT) patients and often has serious consequences. Because of the lack of specificity of diarrheasymptoms cased by Cryptosporidium infection, it is rarely reported in patients undergoing liver transplantation (LT). It frequently delays diagnosis, coming with severe consequences. In clinical work, diagnosing Cryptosporidium infection in LT patients is also complex but single, and the corresponding anti-infective treatment regimen has not yet been standardized. A rare case of septic shock due to a delayed diagnosis of Cryptosporidium infection after LT and relevant literature are discussed in the passage. CASE PRESENTATION: A patient who had received LT for two years was admitted to the hospital with diarrhea more than 20 days after eating an unclean diet. After failing treatment at a local hospital, he was admitted to Intensive Care Unit after going into septic shock. The patient presented hypovolemia due to diarrhea, which progressed to septic shock. The patient's sepsis shock was controlled after receiving multiple antibiotic combinations and fluid resuscitation. However, the persistent diarrhea, as the culprit of the patient's electrolyte disturbance, hypovolemia, and malnutrition, was unsolved. The causative agent of diarrhea, Cryptosporidium infection, was identified by colonoscopy, faecal antacid staining, and blood high-throughput sequencing (NGS). The patient was treated by reducing immunosuppression and Nitazoxanide (NTZ), which proved effective in this case. CONCLUSION: When LT patients present with diarrhea, clinicians should consider the possibility of Cryptosporidium infection, in addition to screening for conventional pathogens. Tests such as colonoscopy, stool antacid staining and blood NGS sequencing can help diagnose and treat of Cryptosporidium infection early and avoid serious consequences of delayed diagnosis. In treating Cryptosporidium infection in LT patients, the focus should be on the patient's immunosuppressive therapy, striking a balance between anti-immunorejection and anti-infection should be sought. Based on practical experience, NTZ therapy in combination with controlled CD4 + T cells at 100-300/mm3 was highly effective against Cryptosporidium without inducing immunorejection.

Intraoperative hypovolemia as a possible precipitating factor for pituitary apoplexy: a case report.

BACKGROUND: Pituitary apoplexy is acute infarction with or without hemorrhage of the pituitary gland. It is a rare but potentially life-threatening emergency that most commonly occurs in the setting of pituitary adenoma. The mechanisms underlying pituitary apoplexy are not well understood, but are proposed to include factors of both hemodynamic supply and adenoma demand. In the case of patients with known pituitary macroadenomas undergoing major surgery for other indications, there is a theoretically increased risk of apoplexy in the setting of "surgical stress." However, risk stratification of patients with nonfunctioning pituitary adenomas prior to major surgery is challenging because the precipitating factors for pituitary apoplexy are not completely understood. Here we present a case in which intraoperative hypovolemia is a possible mechanistic precipitating factor for pituitary apoplexy. CASE PRESENTATION: A 76-year-old patient with a known hypofunctioning pituitary macroadenoma underwent nephrectomy for renal cell carcinoma, during which there was significant intraoperative blood loss. He became symptomatic with ophthalmoplegia on the second postoperative day, and was diagnosed with pituitary apoplexy. He was managed conservatively with cortisol replacement therapy, and underwent therapeutic anticoagulation 2 months after pituitary apoplexy for deep vein thrombosis. His ophthalmoplegia slowly resolved over months of follow-up. Pituitary apoplexy did not recur with therapeutic anticoagulation. CONCLUSIONS: When considering the risk of surgery in patients with a known pituitary macroadenoma, an operation with possible high-volume intraoperative blood loss may have increased risk of pituitary apoplexy because intraoperative hypovolemia may precipitate ischemia, infarction, and subsequent hemorrhage. This may be particularly relevant in the cases of elective surgery. Additionally, we found that we were able to therapeutically anticoagulate a patient 2 months after pituitary apoplexy for the management of deep vein thrombosis without recurrence of pituitary apoplexy.

Phlebotomy resulting in controlled hypovolemia to prevent blood loss in major hepatic resections (PRICE-2): study protocol for a phase 3 randomized controlled trial.

INTRODUCTION: Blood loss and red blood cell (RBC) transfusion in liver surgery are areas of concern for surgeons, anesthesiologists, and patients alike. While various methods are employed to reduce surgical blood loss, the evidence base surrounding each intervention is limited. Hypovolemic phlebotomy, the removal of whole blood from the patient without volume replacement during liver transection, has been strongly associated with decreased bleeding and RBC transfusion in observational studies. This trial aims to investigate whether hypovolemic phlebotomy is superior to usual care in reducing RBC transfusions in liver resection. METHODS: This study is a double-blind multicenter randomized controlled trial. Adult patients undergoing major hepatic resections for any indication will be randomly allocated in a 1:1 ratio to either hypovolemic phlebotomy and usual care or usual care alone. Exclusion criteria will be minor resections, preoperative hemoglobin <100g/L, renal insufficiency, and other contraindication to hypovolemic phlebotomy. The primary outcome will be the proportion of patients receiving at least one allogeneic RBC transfusion unit within 30 days of the onset of surgery. Secondary outcomes will include transfusion of other allogeneic blood products, blood loss, morbidity, mortality, and intraoperative physiologic parameters. The surgical team will be blinded to the intervention. Randomization will occur on the morning of surgery. The sample size will comprise 440 patients. Enrolment will occur at four Canadian academic liver surgery centers over a 4-year period. Ethics approval will be obtained at participating sites before enrolment. DISCUSSION: The results of this randomized control trial will provide high-quality evidence regarding the use of hypovolemic phlebotomy in major liver resection and its effects on RBC transfusion. If proven to be effective, this intervention could become standard of care in liver operations internationally and become incorporated within perioperative patient blood management programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03651154 . Registered on August 29 2018.

Management of Hyperosmolar Hyperglycaemic State (HHS) in Adults: An updated guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care Group.

Hyperosmolar Hyperglycaemic State (HHS) is a medical emergency associated with high mortality. It occurs less frequently than diabetic ketoacidosis (DKA), affects those with pre-existing/new type 2 diabetes mellitus and increasingly affecting children/younger adults. Mixed DKA/HHS may occur. The JBDS HHS care pathway consists of 3 themes (clinical assessment and monitoring, interventions, assessments and prevention of harm) and 5 phases of therapy (0-60 min, 1-6, 6-12, 12-24 and 24-72 h). Clinical features of HHS include marked hypovolaemia, osmolality ≥320 mOsm/kg using [(2×Na+ ) + glucose+urea], marked hyperglycaemia ≥30 mmol/L, without significant ketonaemia (≤3.0 mmol/L), without significant acidosis (pH >7.3) and bicarbonate ≥15 mmol/L. Aims of the therapy are to improve clinical status/replace fluid losses by 24 h, gradual decline in osmolality (3.0-8.0 mOsm/kg/h to minimise the risk of neurological complications), blood glucose 10-15 mmol/L in the first 24 h, prevent hypoglycaemia/hypokalaemia and prevent harm (VTE, osmotic demyelination, fluid overload, foot ulceration). Underlying precipitants must be identified and treated. Interventions include: (1) intravenous (IV) 0.9% sodium chloride to restore circulating volume (fluid losses 100-220 ml/kg, caution in elderly), (2) fixed rate intravenous insulin infusion (FRIII) should be commenced once osmolality stops falling with fluid replacement unless there is ketonaemia (FRIII should be commenced at the same time as IV fluids). (3) glucose infusion (5% or 10%) should be started once glucose <14 mmol/L and (4) potassium replacement according to potassium levels. HHS resolution criteria are: osmolality <300 mOsm/kg, hypovolaemia corrected (urine output ≥0.5 ml/kg/h), cognitive status returned to pre-morbid state and blood glucose <15 mmol/L.

[Reconstruction of caval veins]. / Rekonstruktsiya polykh ven.

OBJECTIVE: To study the possibilities and results of reconstruction of caval veins. MATERIAL AND METHODS: We analyzed the results of reconstruction of caval veins in 31 patients (19 men and 12 women) including superior vena cava (SVC) in 5 cases and inferior vena cava (IVC) in 26 cases. Penetrating wounds with vascular damage were found in 8 patients. Iatrogenic damage to IVC was observed in 19 patients (nephrectomy for kidney cancer - 2, nephrectomy for secondary kidney wrinkling - 1, echinococcectomy from retroperitoneal space - 1, adrenalectomy for adrenal tumors - 5, right-sided lumbar sympathectomy - 1, resection of abdominal aortic aneurysm - 1, resection of a large retroperitoneal tumor - 6). Iatrogenic damage to SVC occurred in 2 patients during resection of mediastinal tumor. In other 4 cases, elective surgery for mediastinal tumor (1), pancreatic head cancer (2) and liver alveococcosis (1) was accompanied by resection and replacement of caval veins. RESULTS: All interventions for caval vein injury were performed under adequate infusion therapy. Seven (22.6%) patients died. One patient with blunt chest trauma and damage to SVC died during thoracotomy. In another patient, infrarenal IVC was intersected during mobilization of retroperitoneal hydatid cyst that required ligation for vital indications. High venous hypertension below the ligature led to eruption of sutures on the venous stump. The patient died from hypovolemia after additional IVC ligation. Other 5 patients died in early postoperative period without leaving the state of shock. These patients had damage to retrohepatic segment of IVC (1), vascular-organ (1) and iatrogenic (3) injuries. One patient died from pulmonary embolism, two patients - from venous bleeding between the 2nd and the 5th postoperative days. Patients died before reoperations. Two patients with postoperative bleeding underwent redo surgery with favorable outcomes. One patient underwent redo surgery for peritonitis with a favorable result. Thus, 7 (22.6%) patients with caval vein injury died in intraoperative and early postoperative period. Non-specific complications occurred in 4 (12.9%) patients. These events were corrected by conservative measures. Other 24 (77.4%) patients with traumatic and iatrogenic injuries of caval veins were discharged. CONCLUSION: Caval vein injury is less common event compared to other vascular damages. Nevertheless, this complication is accompanied by severe blood loss, shock and hypovolemia. We can only assume damage to a great vessel in patients with penetrating wounds before surgery and appropriate symptoms of internal bleeding. However, final diagnosis is made during surgery. Hemostasis is a responsible and difficult surgical stage in these patients. There is usually no alternative to reconstructive surgery in these cases. However, ligation is permissible in extremely ill patients and only in infrarenal segment of IVC. Vascular suture is a more acceptable and effective option for reconstruction. However, patch repair is advisable for large defects. In our opinion, this approach is better regarding long-term patency compared to total replacement with synthetic prostheses.

Reliability of Pre-Induction Inferior Vena Cava Assessment with Ultrasound for the Prediction of Post-Induction Hypotension in Neurosurgical Patients Undergoing Intracranial Surgery.

Background: Hypotension is one of the most common complications following induction of general anesthesia. Preemptive diagnosis and correcting the hypovolemic status can reduce the incidence of post-induction hypotension. However, an association between preoperative volume status and severity of post-induction hypotension has not been established in neurosurgical patients. We hypothesized that preoperative ultrasonographic assessment of intravascular volume status can be used to predict post-induction hypotension in neurosurgical patients. Our study objective was to establish the relationship between pre-induction maximum inferior vena cava (IVC) diameter, collapsibility index (CI), and post-induction reduction in mean arterial blood pressure in neurosurgical patients. Materials and Methods: A prospective observational study was conducted including 100 patients undergoing elective intracranial surgeries. IVC assessment was done before induction of general anesthesia. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff values of maximum and minimum IVC diameter (IVCDmax and IVCDmin, respectively) and CI for prediction of hypotension. Results: Post-induction hypotension was observed in 41% patients. Patients with small IVCDmax and higher CI% developed hypotension. The areas under the ROC curve (AUCs) were 0.64 (0.53-0.75) for IVCDmax and 0.69 (0.59-0.80) for IVCDmin. The optimal cutoff values were1.38 cm for IVCDmax and 0.94 cm for IVCDmin. The AUC for CI was 0.65 (0.54-0.77) and the optimal cutoff value was 37.5%. Conclusion: Pre-induction IVC assessment with ultrasound is a reliable method to predict post-induction hypotension resulting from hypovolemia in neurosurgical patients.

PragmaTic, prospEctive, randomized, controlled, double-blind, mulTi-centre, multinational study on the safety and efficacy of a 6% HydroxYethyl Starch (HES) solution versus an electrolyte solution in trauma patients: study protocol for the TETHYS study.

BACKGROUND: Trauma may be associated with significant to life-threatening blood loss, which in turn may increase the risk of complications and death, particularly in the absence of adequate treatment. Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss to maintain or re-establish hemodynamic stability with the ultimate goal to avoid organ hypoperfusion and cardiovascular collapse. The current study compares a 6% HES 130 solution (Volulyte 6%) versus an electrolyte solution (Ionolyte) for volume replacement therapy in adult patients with traumatic injuries, as requested by the European Medicines Agency to gain more insights into the safety and efficacy of HES in the setting of trauma care. METHODS: TETHYS is a pragmatic, prospective, randomized, controlled, double-blind, multicenter, multinational trial performed in two parallel groups. Eligible consenting adults ≥ 18 years, with an estimated blood loss of ≥ 500 ml, and in whom initial surgery is deemed necessary within 24 h after blunt or penetrating trauma, will be randomized to receive intravenous treatment at an individualized dose with either a 6% HES 130, or an electrolyte solution, for a maximum of 24 h or until reaching the maximum daily dose of 30 ml/kg body weight, whatever occurs first. Sample size is estimated as 175 patients per group, 350 patients total (α = 0.025 one-tailed, power 1-ß = 0.8). Composite primary endpoint evaluated in an exploratory manner will be 90-day mortality and 90-day renal failure, defined as AKIN stage ≥ 2, RIFLE injury/failure stage, or use of renal replacement therapy (RRT) during the first 3 months. Secondary efficacy and safety endpoints are fluid administration and balance, changes in vital signs and hemodynamic status, changes in laboratory parameters including renal function, coagulation, and inflammation biomarkers, incidence of adverse events during treatment period, hospital, and intensive care unit (ICU) length of stay, fitness for ICU or hospital discharge, and duration of mechanical ventilation and/or RRT. DISCUSSION: This pragmatic study will increase the evidence on safety and efficacy of 6% HES 130 for treatment of hypovolemia secondary to acute blood loss in trauma patients. TRIAL REGISTRATION: Registered in EudraCT, No.: 2016-002176-27 (21 April 2017) and ClinicalTrials.gov, ID: NCT03338218 (09 November 2017).

Identifying critical DO2 with compensatory reserve during simulated hemorrhage in humans.

BACKGROUND: Based on previous experiments in nonhuman primates, we hypothesized that DO2 crit in humans is 5-6 ml O2 ·kg-1  min-1 . STUDY DESIGN AND METHODS: We measured the compensatory reserve (CRM) and calculated oxygen delivery (DO2 ) in 166 healthy, normotensive, nonsmoking subjects (97 males, 69 females) during progressive central hypovolemia induced by lower body negative pressure as a model of ongoing hemorrhage. Subjects were classified as having either high tolerance (HT; N = 111) or low tolerance (LT; N = 55) to central hypovolemia. RESULTS: HT and LT groups were matched for age, weight, BMI, and vital signs, DO2 and CRM at baseline. The CRM-DO2 relationship was best fitted to a logarithmic model in HT subjects (amalgamated R2  = 0.971) and a second-order polynomial model in the LT group (amalgamated R2  = 0.991). Average DO2 crit for the entire subject cohort was estimated at 5.3 ml O2 ·kg-1  min-1 , but was ~14% lower in HT compared with LT subjects. The reduction in DO2 from 40% CRM to 20% CRM was 2-fold greater in the LT compared with the HT group. CONCLUSIONS: Average DO2 crit in humans is 5.3 ml O2 ·kg-1  min-1 , but is ~14% lower in HT compared with LT subjects. The CRM-DO2 relationship is curvilinear in humans, and different when comparing HT and LT individuals. The threshold for an emergent monitoring signal should be recalibrated from 30% to 40% CRM given that the decline in DO2 from 40% CRM to 20% CRM for LT subjects is located on the steepest part of the CRM-DO2 relationship.

A wireless ultrasound patch detects mild-to-moderate central hypovolemia during lower body negative pressure.

BACKGROUND: We have developed a wireless, wearable Doppler ultrasound system that continuously measures the common carotid artery Doppler pulse. A novel measure from this device, the Doppler shock index, accurately detected moderate-to-severe central blood volume loss in a human hemorrhage model generated by lower body negative pressure. In this analysis, we tested whether the wearable Doppler could identify only mild-to-moderate central blood volume loss. METHODS: Eleven healthy volunteers were recruited and studied in a physiology laboratory at the Mayo Clinic. Each participant underwent a lower body negative protocol in duplicate. Carotid Doppler measures including Doppler shock indices were compared with blood pressure and the shock index for their ability to detect both 10% and 20% reductions in stroke volume. RESULTS: All carotid Doppler measures were better able to detect diminishing stroke volume than either systolic or mean arterial pressure. Falling carotid artery corrected flow time and rising heart rate/corrected flow time (DSI FTc ) were the most sensitive measures for detecting 10% and 20% stroke volume reductions, respectively. The area under the receiver operator curves (AUROCs) for all shock indices was at least 0.86; however, the denominators of the two Doppler shock indices (i.e., the corrected flow time and velocity time integral) had AUROCs ranging between 0.81 and 0.9, while the denominator of the traditional shock index (i.e., systolic blood pressure) had AUROCs between 0.54 and 0.7. CONCLUSION: The wearable Doppler ultrasound was able to continuously measure the common carotid artery Doppler pulse. Carotid Doppler measures were highly sensitive at detecting both 10% and 20% stroke volume reduction. All shock indices performed well in their diagnostic ability to measure mild-to-moderate central volume loss, although the denominators of both Doppler shock indices individually outperformed the denominator of the traditional shock index. LEVEL OF EVIDENCE: Diagnostic test or criteria; Level III.

Analysis of effects of acute hypovolemia on arterial stiffness in rabbits monitored with cardio-ankle vascular index.

Although elasticity of the conduit arteries is known to be contribute effective peripheral circulation via Windkessel effects, the relationship between changes in intra-aortic blood volume and conduit artery elasticity remains unknown. Here we assessed the effects of change in intra-aortic blood volume induced by blood removal and subsequent blood transfusion on arterial stiffness and the involvement of autonomic nervous activity using our established rabbit model in the presence or absence of the ganglion blocker hexamethonium (100 mg/kg). Blood removal at a rate of 1 mL/min gradually decreased the blood pressure and blood flow of the common carotid artery but increased a stiffness indicator the cardio-ankle vascular index, which was equally observed in the presence of hexamethonium. These results suggest that arterial stiffness acutely responds to changes in intra-aortic blood volume independent of autonomic nervous system modification.

The pathophysiology of uncontrolled hemorrhage in horses.

BACKGROUND: Hemorrhagic shock in horses may be classified in several ways. Hemorrhage may be considered internal versus external, controlled or uncontrolled, or described based on the severity of hypovolemic shock the patient is experiencing. Regardless of the cause, as the severity of hemorrhage worsens, homeostatic responses are stimulated to ameliorate the systemic and local effects of an oxygen debt. In mild to moderate cases of hemorrhage (<15% blood volume loss), physiological adaptations in the patient may not be clinically apparent. As hemorrhage worsens, often in the uncontrolled situation such as a vascular breach internally, the pathophysiological consequences are numerous. The patient mobilizes fluid and reserve blood volume, notably splenic stored and peripherally circulating erythrocytes, to preferentially supply oxygen to sensitive organs such as the brain and heart. When the global and local delivery of oxygen is insufficient to meet the metabolic needs of the tissues, a cascade of cellular, tissue, and organ dysfunction occurs. If left untreated, the patient dies of hemorrhagic anemic shock. CLINICAL IMPORTANCE: An understanding of the pathophysiological consequences of hemorrhagic shock in horses and their clinical manifestations may help the practitioner understand the severity of blood volume loss, the need for referral, the need for transfusion, and potential outcome. In cases of severe acute uncontrolled hemorrhage, it is essential to recognize the clinical manifestations quickly to best treat the patient, which may include humane euthanasia. KEY POINTS: Uncontrolled hemorrhage may be defined as the development of a vascular breach and hemorrhage that cannot be controlled by interventional hemostasis methods such as external pressure, tourniquet, or ligation. Causes of uncontrolled hemorrhage in horses may be due to non-surgical trauma, surgical trauma, invasive diagnostic procedures including percutaneous organ biopsy, coagulopathy, hypertension, cardiovascular anomaly, vascular damage, neoplasia such as hemangiosarcoma, toxicity, or idiopathic in nature. When a critical volume of blood is lost, the respondent changes in heart rate, splenic blood mobilization, and microcirculatory control can no longer compensate for decreasing oxygen delivery to the tissues In spite of organ-specific microvascular responses (eg, myogenic responses, local mediator modulation of microvasculature, etc), all organs experience decreases in blood flow during severe hypovolemia Acute, fatal hemorrhagic shock is characterized by progressive metabolic acidosis, coagulopathy, and hypothermia, often termed the "triad of death," followed by circulatory collapse.

Open chest selective aortic arch perfusion vs open cardiac massage as a means of perfusion during in exsanguination cardiac arrest: a comparison of coronary hemodynamics in swine.

AIM: To describe and compare the aortic-right atrial pressure (AoP-RAP) gradients and mean coronary perfusion pressures (CPPs) generated during open chest selective aortic arch perfusion (OCSAAP) with those generated during open cardiac massage (OCM) in hypovolemic swine. METHODS: Ten male Hanford swine utilized in a prior poly-trauma study were included in the study. Animals were rendered hypovolemic via a 30% volume bleed. Upon confirmation of death, animals underwent immediate clamshell thoracotomy and aortic cross-clamping followed by 5 min of OCM. A catheter suitable for OCSAAP was then inserted into the aorta and animals underwent 1 min of OCSAAP at a rate of 10 mL/kg/min. Aortic and right atrial pressures were recorded continuously using solid-state blood pressure catheters. Representative 10-s intervals from each resuscitation method were extracted. Hemodynamic parameters including AoP-RAP gradients and CPPs were calculated and compared. RESULTS: At baseline, time from death to intervention was significantly shorter for OCM. However, mean CPPs and AoP-RAP gradients were significantly higher in animals undergoing OCSAAP. 98% of OCSAAP segments had a mean CPP > 15, compared to 35% of OCM intervals. While OCM had a significant negative correlation between time to intervention and maximum CPP, this correlation was not significant for OCSAAP. CONCLUSION: OCSAAP generates favorable and potentially time-resistant pressure gradients when compared to those generated by OCM. Further investigation of the technique of OCSAAP is warranted, as it may have potential utility as a therapy during resuscitative thoracotomy (RT).

AVP-eGFP was significantly upregulated by hypovolemia in the parvocellular division of the paraventricular nucleus in the transgenic rats.

Arginine vasopressin (AVP) is produced in the paraventricular (PVN) and supraoptic nuclei (SON). Peripheral AVP, which is secreted from the posterior pituitary, is produced in the magnocellular division of the PVN (mPVN) and SON. In addition, AVP is produced in the parvocellular division of the PVN (pPVN), where corticotrophin-releasing factor (CRF) is synthesized. These peptides synergistically modulate the hypothalamic-pituitary-adrenal (HPA) axis. Previous studies have revealed that the HPA axis was activated by hypovolemia. However, the detailed dynamics of AVP in the pPVN under hypovolemic state has not been elucidated. Here, we evaluated the effects of hypovolemia and hyperosmolality on the hypothalamus, using AVP-enhanced green fluorescent protein (eGFP) transgenic rats. Polyethylene glycol (PEG) or 3% hypertonic saline (HTN) was intraperitoneally administered to develop hypovolemia or hyperosmolality. AVP-eGFP intensity was robustly upregulated at 3 and 6 h after intraperitoneal administration of PEG or HTN in the mPVN. While in the pPVN, eGFP intensity was significantly increased at 6 h after intraperitoneal administration of PEG with significant induction of Fos-immunoreactive (-ir) neurons. Consistently, eGFP mRNA, AVP hnRNA, and CRF mRNA in the pPVN and plasma AVP and corticosterone were significantly increased at 6 h after intraperitoneal administration of PEG. The results suggest that AVP and CRF syntheses in the pPVN were activated by hypovolemia, resulting in the activation of the HPA axis.

The alteration of neuronal activities of the cuneiform nucleus in non-hypovolemic and hypovolemic hypotensive conditions / Alterações da atividade neuronal no núcleo cuneiforme em condições hipovolêmicas e não hipovolêmicas

Abstract Background: The cuneiform nucleus is located in the center of the circuit that mediates autonomic responses to stress. Hemorrhagic hypotension leads to chemoreceptor anoxia, which consequently results in the reduction of baroreceptor discharge and stimulation of the chemoreceptor. Objective: Using the single-unit recording technique, the neuronal activities of the cuneiform nucleus were investigated in hypotensive states induced by hemorrhage and administration of an anti-hypertensive drug (hydralazine). Methods: Thirty male rats were divided into the control, hemorrhage, and hydralazine groups. The femoral artery was cannulated for the recording of cardiovascular responses, including systolic blood pressure, mean arterial pressure, and heart rate. Hydralazine was administered via tail vein. The single-unit recording was performed from the cuneiform nucleus. Results: The maximal systolic blood pressure and the mean arterial pressure significantly decreased and heart rate significantly increased after the application of hydralazine as well as the following hemorrhage compared to the control group. Hypotension significantly increased the firing rate of the cuneiform nucleus in both the hemorrhage and hydralazine groups compared to the control group. Conclusions: The present data indicate that the cuneiform nucleus activities following hypotension may play a crucial role in blood vessels and vasomotor tone.

RESUMO Antecedentes: O núcleo cuneiforme está localizado no centro do circuito que media as respostas autonômicas ao estresse. A hipotensão hemorrágica leva à anóxia dos quimiorreceptores, que, consequentemente, resulta na redução da descarga dos barorreceptores e estimulação do quimiorreceptor. Objetivo: Utilizando a técnica de registro em unidade única, as atividades neuronais do núcleo cuneiforme foram investigadas em estados de hipotensão induzida por hemorragia e administração de um anti-hipertensivo (hidralazina). Métodos: Trinta ratos machos foram divididos nos grupos controle, hemorragia e hidralazina. A artéria femoral foi canulada, para o registro de respostas cardiovasculares, incluindo pressão arterial sistólica, pressão arterial média e frequência cardíaca. A hidralazina foi administrada na veia da cauda. O registro de unidade única foi realizado a partir do núcleo cuneiforme. Resultados: A pressão arterial sistólica máxima e a pressão arterial média diminuíram significativamente, e a frequência cardíaca aumentou significativamente após a aplicação de hidralazina, bem como a hemorragia seguinte, em comparação com o grupo controle. A hipotensão aumentou significativamente a taxa de disparo da população do núcleo cuneiforme em ambos os grupos de hemorragia e hidralazina, em comparação com o grupo de controle. Conclusões: Os presentes dados indicam que as atividades do núcleo cuneiforme após hipotensão podem desempenhar um papel crucial nos vasos sanguíneos e no tônus vasomotor.