Population Kinetics of 0.9% Saline Distribution in Hemorrhaged Awake and Isoflurane-anesthetized Volunteers.

BACKGROUND: Population-based, pharmacokinetic modeling can be used to describe variability in fluid distribution and dilution between individuals and across populations. The authors hypothesized that dilution produced by crystalloid infusion after hemorrhage would be larger in anesthetized than in awake subjects and that population kinetic modeling would identify differences in covariates. METHODS: Twelve healthy volunteers, seven females and five males, mean age 28 ± 4.3 yr, underwent a randomized crossover study. Each subject participated in two separate sessions, separated by four weeks, in which they were assigned to an awake or an anesthetized arm. After a baseline period, hemorrhage (7 ml/kg during 20 min) was induced, immediately followed by a 25 ml/kg infusion during 20 min of 0.9% saline. Hemoglobin concentrations, sampled every 5 min for 60 min then every 10 min for an additional 120 min, were used for population kinetic modeling. Covariates, including body weight, sex, and study arm (awake or anesthetized), were tested in the model building. The change in dilution was studied by analyzing area under the curve and maximum plasma dilution. RESULTS: Anesthetized subjects had larger plasma dilution than awake subjects. The analysis showed that females increased area under the curve and maximum plasma dilution by 17% (with 95% CI, 1.08 to 1.38 and 1.07 to 1.39) compared with men, and study arm (anesthetized increased area under the curve by 99% [0.88 to 2.45] and maximum plasma dilution by 35% [0.71 to 1.63]) impacted the plasma dilution whereas a 10-kg increase of body weight resulted in a small change (less than1% [0.93 to 1.20]) in area under the curve and maximum plasma dilution. Mean arterial pressure was lower in subjects while anesthetized (P < 0.001). CONCLUSIONS: In awake and anesthetized subjects subjected to controlled hemorrhage, plasma dilution increased with anesthesia, female sex, and lower body weight. Neither study arm nor body weight impact on area under the curve or maximum plasma dilution were statistically significant and therefore no effect can be established.

Functional Improvements Utilizing the Short Physical Performance Battery (SPPB) in the Elderly after Epidural Steroid Injections.

PURPOSE OF REVIEW: The treatment of debilitating pain and loss of function secondary to lumbar stenosis is in high demand with the aging patient population. Options, including epidural steroid injections (ESIs) and medication therapy, are limited and it is unclear if they provide any functional improvements. In this prospective study, we evaluate functional outcomes in older adults with symptomatic lumbar stenosis treated with ESIs compared to those managed with medications by introducing the Short Physical Performance Battery (SPPB). Our study was IRB-approved and included 16 patients, 68 to 83 years old, with symptomatic back and radicular leg pain secondary to lumbar stenosis. Patients could elect to undergo a lumbar ESI (n = 11) or be treated via medication management (n = 5). Numeric pain score, SPPB score, and adverse events were measured and compared at baseline and a 1-month follow-up visit. RECENT FINDINGS: Statistically significant improvements were observed from baseline compared to the 1-month follow-up for total SPPB score in the injection group. Similar improvements in the injection group were observed for pain scores and the SPPB subcomponents such as the 4-m walk test, chair stand time, and balance score. Comparatively, no statistically significant improvements were observed in the medication group. Lumbar ESIs improved objective physical capacity parameters and pain scores in elderly patients with symptomatic lumbar stenosis compared to medication management. In addition, the SPPB is an easy-to-use tool to measure changes in physical function in older adults and could easily be integrated into an outpatient pain clinic.

Closed-Loop- and Decision-Assist-Guided Fluid Therapy of Human Hemorrhage.

OBJECTIVES: We sought to evaluate the efficacy, efficiency, and physiologic consequences of automated, endpoint-directed resuscitation systems and compare them to formula-based bolus resuscitation. DESIGN: Experimental human hemorrhage and resuscitation. SETTING: Clinical research laboratory. SUBJECTS: Healthy volunteers. INTERVENTIONS: Subjects (n = 7) were subjected to hemorrhage and underwent a randomized fluid resuscitation scheme on separate visits 1) formula-based bolus resuscitation; 2) semiautonomous (decision assist) fluid administration; and 3) fully autonomous (closed loop) resuscitation. Hemodynamic variables, volume shifts, fluid balance, and cardiac function were monitored during hemorrhage and resuscitation. Treatment modalities were compared based on resuscitation efficacy and efficiency. MEASUREMENTS AND MAIN RESULTS: All approaches achieved target blood pressure by 60 minutes. Following hemorrhage, the total amount of infused fluid (bolus resuscitation: 30 mL/kg, decision assist: 5.6 ± 3 mL/kg, closed loop: 4.2 ± 2 mL/kg; p < 0.001), plasma volume, extravascular volume (bolus resuscitation: 17 ± 4 mL/kg, decision assist: 3 ± 1 mL/kg, closed loop: -0.3 ± 0.3 mL/kg; p < 0.001), body weight, and urinary output remained stable under decision assist and closed loop and were significantly increased under bolus resuscitation. Mean arterial pressure initially decreased further under bolus resuscitation (-10 mm Hg; p < 0.001) and was lower under bolus resuscitation than closed loop at 20 minutes (bolus resuscitation: 57 ± 2 mm Hg, closed loop: 69 ± 4 mm Hg; p = 0.036). Colloid osmotic pressure (bolus resuscitation: 19.3 ± 2 mm Hg, decision assist, closed loop: 24 ± 0.4 mm Hg; p < 0.05) and hemoglobin concentration were significantly decreased after bolus fluid administration. CONCLUSIONS: We define efficacy of decision-assist and closed-loop resuscitation in human hemorrhage. In comparison with formula-based bolus resuscitation, both semiautonomous and autonomous approaches were more efficient in goal-directed resuscitation of hemorrhage. They provide favorable conditions for the avoidance of over-resuscitation and its adverse clinical sequelae. Decision-assist and closed-loop resuscitation algorithms are promising technological solutions for constrained environments and areas of limited resources.

Co-administration of vancomycin and piperacillin-tazobactam is associated with increased renal dysfunction in adult and pediatric burn patients.

BACKGROUND: Burn patients are prone to infections which often necessitate broad antibiotic coverage. Vancomycin is a common antibiotic after burn injury and is administered alone (V), or in combination with imipenem-cilastin (V/IC) or piperacillin-tazobactam (V/PT). Sparse reports indicate that the combination V/PT is associated with increased renal dysfunction. The purpose of this study was to evaluate the short-term impact of the three antibiotic administration types on renal dysfunction. METHODS: All pediatric and adult patients admitted to our centers between 2004 and 2016 with a burn injury were included in this retrospective review if they met the criteria of exposition to either V, V/IC, or V/PT for at least 48 h, had normal baseline creatinine, and no pre-existing renal dysfunction. Creatinine was monitored for 7 days after initial exposure; the absolute and relative increase was calculated, and patient renal outcomes were classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria depending on creatinine increases and estimated creatinine clearance. Secondary endpoints (demographic and clinical data, incidences of septicemia, and renal replacement therapy) were analyzed. Antibiotic doses were modeled in logistic and linear multivariable regression models to predict categorical KDIGO events and relative creatinine increase. RESULTS: Out of 1449 patients who were screened, 718 met the inclusion criteria, 246 were adults, and 472 were children. Between the study cohorts V, V/IC, and V/PT, patient characteristics at admission were comparable. V/PT administration was associated with a statistically higher serum creatinine, and lower creatinine clearance compared to patients receiving V alone or V/IC in adults and children after burn injury. The incidence of KDIGO stages 1, 2, and 3 was higher after V/PT treatment. In children, the incidence of KDIGO stage 3 following administration of V/PT was greater than after V/IC. In adults, the incidence of renal replacement therapy was higher after V/PT compared with V or V/IC. Multivariate modeling demonstrated that V/PT is an independent predictor of renal dysfunction. CONCLUSION: Co-administration of vancomycin and piperacillin-tazobactam is associated with increased renal dysfunction in pediatric and adult burn patients when compared to vancomycin alone or vancomycin plus imipenem-cilastin. The mechanism of this increased nephrotoxicity remains elusive and warrants further scientific evaluation.

Physician-Directed Versus Computerized Closed-Loop Control of Blood Pressure Using Phenylephrine in a Swine Model.

BACKGROUND: Vasopressors provide a rapid and effective approach to correct hypotension in the perioperative setting. Our group developed a closed-loop control (CLC) system that titrates phenylephrine (PHP) based on the mean arterial pressure (MAP) during general anesthesia. As a means of evaluating system competence, we compared the performance of the automated CLC with physicians. We hypothesized that our CLC algorithm more effectively maintains blood pressure at a specified target with less blood pressure variability and reduces the dose of PHP required. METHODS: In a crossover study design, 6 swine under general anesthesia were subjected to a normovolemic hypotensive challenge induced by sodium nitroprusside. The physicians (MD) manually changed the PHP infusion rate, and the CLC system performed this task autonomously, adjusted every 3 seconds to achieve a predetermined MAP. RESULTS: The CLC maintained MAP within 5 mm Hg of the target for (mean ± standard deviation) 93.5% ± 3.9% of the time versus 72.4% ± 26.8% for the MD treatment (P = .054). The mean (standard deviation) percentage of time that the CLC and MD interventions were above target range was 2.1% ± 3.3% and 25.8% ± 27.4% (P = .06), respectively. Control statistics, performance error, median performance error, and median absolute performance error were not different between CLC and MD interventions. PHP infusion rate adjustments by the physician were performed 12 to 80 times in individual studies over a 60-minute period. The total dose of PHP used was not different between the 2 interventions. CONCLUSIONS: The CLC system performed as well as an anesthesiologist totally focused on MAP control by infusing PHP. Computerized CLC infusion of PHP provided tight blood pressure control under conditions of experimental vasodilation.

Correlation Between PaO2/FIO2 and Peripheral Capillary Oxygenation/FIO2 in Burned Children With Smoke Inhalation Injury.

OBJECTIVES: Determine whether the peripheral capillary oxygenation/FIO2 ratio correlates with the PaO2/FIO2 ratio in burned children with smoke inhalation injury, with the goal of understanding if the peripheral capillary oxygenation/FIO2 ratio can serve as a surrogate for the PaO2/FIO2 ratio for the diagnosis of acute respiratory distress syndrome. DESIGN: Retrospective chart review. SETTING: Shriners Hospitals for Children-Galveston. PATIENTS: All burned children with smoke inhalation injury who were admitted from 1996 to 2014 and had simultaneously obtained peripheral capillary oxygenation, FIO2 and PaO2 measurements. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred seventy-three patients (63% male, 8 ± 5 yr, 53% ± 24% total body surface area burns) were analyzed. Peripheral capillary oxygenation/FIO2 ratios were divided into four subgroups based on peripheral capillary oxygenation values (≤ 100%, ≤ 98%, ≤ 95%, and ≤ 92%). Significance was accepted at r greater than 0.81. The r (number of matches) was 0.66 (23,072) for less than or equal to 100%, 0.87 (18,932) for less than or equal to 98%, 0.89 (7,056) for less than or equal to 95%, and 0.93 (4,229) for less than or equal to 92%. In the subgroup of patients who developed acute respiratory distress syndrome, r was 0.65 (8,357) for less than or equal to 100%, 0.89 (7,578) for less than or equal to 98%, 0.89 (4,115) for less than or equal to 95%, and 0.91 (2,288) less than or equal to 92%. CONCLUSIONS: PaO2/FIO2 and peripheral capillary oxygenation/FIO2 strongly correlate in burned children with smoke inhalation injury, with a peripheral capillary oxygenation of less than 92% providing the strongest correlation. Thus, peripheral capillary oxygenation/FIO2 ratio may be able to serve as surrogate for PaO2/FIO2, especially when titrating FIO2 to achieve a peripheral capillary oxygenation of 90-95% (i.e., in the acute respiratory distress syndrome range).

The physiologic responses to a fluid bolus administration in old and young healthy adults.

BACKGROUND: Organ function is known to decline with age. Optimizing cardiac, pulmonary and renal function in older adults has led to significant improvements in perioperative care. However, when substantial blood loss and fluid shifts occur, perioperative outcomes still remains poor, especially in older adults. We suspect that this could be due to age-related changes in endothelial function-an organ controlling the transport of fluid and solutes. The capillary filtration coefficient (CFC) is an important determinant of fluid transport. The CFC can be measured in vivo, which provides a tool to estimate endothelial barrier function. We have previously shown that the CFC increases when giving a fluid bolus resulting in increased vascular and extravascular volume expansion, in young adults. This study aimed to compare the physiologic determinants of fluid distribution in young versus older adults so that clinicians can best optimize perioperative fluid therapy. METHODS: Ten healthy young volunteers (ages 21-35) and nine healthy older volunteers (ages 60-75) received a 10 mL/kg fluid bolus over the course of twenty minutes. Hemodynamics, systolic and diastolic heart function, fluid volumetrics and microcirculatory determinants were measured before, during, and after the fluid bolus. RESULTS: Diastolic function was reduced in older versus younger adults before and after fluid bolus (P < 0.01). Basal CFC and plasma oncotic pressure were lower in the older versus younger adults. Further, CFC did not increase in older adults following the fluid bolus, whereas it did in younger adults (p < 0.05). Cumulative urinary output, while lower in older adults, was not significantly different (p = 0.059). Mean arterial pressure and systemic vascular resistance were elevated in the older versus younger adults (p < 0.05). CONCLUSION: Older adults show a less reactive CFC to a fluid bolus, which could reduce blood to tissue transport of fluid. Diastolic dysfunction likely contributes to fluid maldistribution in older adults.

Muscle protein metabolism responds similarly to exogenous amino acids in healthy younger and older adults during NO-induced hyperemia.

The combination of increasing blood flow and amino acid (AA) availability provides an anabolic stimulus to the skeletal muscle of healthy young adults by optimizing both AA delivery and utilization. However, aging is associated with a blunted response to anabolic stimuli and may involve impairments in endothelial function. We investigated whether age-related differences exist in the muscle protein anabolic response to AAs between younger (30 ± 2 yr) and older (67 ± 2 yr) adults when macrovascular and microvascular leg blood flow were similarly increased with the nitric oxide (NO) donor, sodium nitroprusside (SNP). Regardless of age, SNP+AA induced similar increases above baseline (P ≤ 0.05) in macrovascular flow (4.3 vs. 4.4 ml·min(-1)·100 ml leg(-1) measured using indocyanine green dye dilution), microvascular flow (1.4 vs. 0.8 video intensity/s measured using contrast-enhanced ultrasound), phenylalanine net balance (59 vs. 68 nmol·min(-1)·100 ml·leg(-1)), fractional synthetic rate (0.02 vs. 0.02%/h), and model-derived muscle protein synthesis (62 vs. 49 nmol·min(-1)·100 ml·leg(-1)) in both younger vs. older individuals, respectively. Provision of AAs during NO-induced local skeletal muscle hyperemia stimulates skeletal muscle protein metabolism in older adults to a similar extent as in younger adults. Our results suggest that the aging vasculature is responsive to exogenous NO and that there is no age-related difference per se in AA-induced anabolism under such hyperemic conditions.

Transpulmonary thermodilution for hemodynamic measurements in severely burned children.

INTRODUCTION: Monitoring of hemodynamic and volumetric parameters after severe burns is of critical importance. Pulmonary artery catheters, however, have been associated with many risks. Our aim was to show the feasibility of continuous monitoring with minimally invasive transpulmonary thermodilution (TPTD) in severely burned pediatric patients. METHODS: This prospective cohort study was conducted in patients with severe burns over 40% of the total body surface area (TBSA) who were admitted to the hospital within 96 hours after sustaining the injury. TPTD measurements were performed using the PiCCO system (Pulsion Medical Systems, Munich, Germany). Cardiac Index (CI), Intrathoracic Blood Volume Index (ITBVI) (Stewart-Hamilton equation), Extravascular Lung Water Index (EVLWI) and Systemic Vascular Resistance Index (SVRI) measurements were recorded twice daily. Statistical analysis was performed using one-way repeated measures analysis of variance with the post hoc Bonferroni test for intra- and intergroup comparisons. RESULTS: Seventy-nine patients with a mean age (±SD) of 9 ± 5 years and a mean TBSA burn (±SD) of 64% ± 20% were studied. CI significantly increased compared to level at admission and was highest 3 weeks postburn. ITBVI increased significantly starting at 8 days postburn. SVRI continuously decreased early in the perioperative burn period. EVLWI increased significantly starting at 9 days postburn. Young children (0 to 5 years old) had a significantly increased EVLWI and decreased ITBVI compared to older children (12 to 18 years old). EVLWI was significantly higher in patients who did not survive burn injury. CONCLUSIONS: Continuous PiCCO measurements were performed for the first time in a large cohort of severely burned pediatric patients. The results suggest that hyperdynamic circulation begins within the first week after burn injury and continues throughout the entire intensive care unit stay.

Cardiac Dysfunction in Severely Burned Patients: Current Understanding of Etiology, Pathophysiology, and Treatment.

Patients who experience severe burn injuries face a massive inflammatory response resulting in hemodynamic and cardiovascular complications. Even after immediate and appropriate resuscitation, removal of burn eschar and covering of open areas, burn patients remain at high risk for serious morbidity and mortality. As a result of the massive fluid shifts following the initial injury, along with large volume fluid resuscitation, the cardiovascular system is critically affected. Further, increased inflammation, catecholamine surge, and hypermetabolic syndrome impact cardiac dysfunction, which worsens outcomes of burn patients. This review aimed to summarize the current knowledge about the effect of burns on the cardiovascular system.A comprehensive search of the PubMed and Embase databases and manual review of articles involving effects of burns on the cardiovascular system was conducted.Many burn units use multimodal monitors (e.g., transpulmonary thermodilution) to assess hemodynamics and optimize cardiovascular function. Echocardiography is often used for additional evaluations of hemodynamically unstable patients to assess systolic and diastolic function. Due to its noninvasive character, echocardiography can be repeated easily, which allows us to follow patients longitudinally.The use of anabolic and anticatabolic agents has been shown to be beneficial for short- and long-term outcomes of burn survivors. Administration of propranolol (non-selective ß-receptor antagonist) or oxandrolone (synthetic testosterone) for up to 12 months post-burn counteracts hypermetabolism during hospital stay and improves cardiac function.A comprehensive understanding of how burns lead to cardiac dysfunction and new therapeutic options could contribute to better outcomes in this patient population.

Simulating Surgical Skills in Animals: Systematic Review, Costs & Acceptance Analyses.

Background: Modern surgery demands high-quality and reproducibility. Due to new working directives, resident duty hours have been restricted and evidence exists that pure on-the-job training provides insufficient exposure. We hypothesize that supplemental simulations in animal models provide a realistic training to augment clinical experiences. This study reviews surgical training models, their costs and survey results illustrating academic acceptance. Methods: Animal models were identified by literature research. Costs were analyzed from multiple German and Austrian training programs. A survey on their acceptance was conducted among faculty and medical students. Results: 915 articles were analyzed, thereof 91 studies described in-vivo animal training models, predominantly for laparoscopy (30%) and microsurgery (24%). Cost-analysis revealed single-training costs between 307€ and 5,861€ depending on model and discipline. Survey results illustrated that 69% of the participants had no experience, but 66% would attend training under experienced supervision. Perceived public acceptance was rated intermediate by medical staff and students (4.26; 1-low, 10 high). Conclusion: Training in animals is well-established and was rated worth attending in a majority of a representative cohort to acquire key surgical skills, in light of reduced clinical exposure. Animal models may therefore supplement the training of tomorrow's surgeons to overcome limited hands-on experience until virtual simulations can provide such educational tools.

Blood Loss and Visibility with Esmolol vs Labetalol in Endoscopic Sinus Surgery: A Randomized Clinical Trial.

OBJECTIVES: Improved intraoperative visibility during functional endoscopic sinus surgery (FESS) decreases the risk of serious orbital or skull base injuries. Esmolol and labetalol have been used to reduce bleeding and achieve better visibility, but it remains unclear which drug is more effective. This study aims to measure visibility scores and mucosal bleeding rates for esmolol and labetalol in FESS. METHODS: This is a 1-year randomized double-blind trial of adults undergoing FESS at a tertiary academic center. The inclusion criteria were as follows: age 18 or older; history of chronic rhinosinusitis (CRS) with or without nasal polyps; undergoing FESS for CRS; and American Society of Anesthesiologists (ASA) physical status 1 (healthy) or 2 (patient with mild systemic disease). The exclusion criteria were as follows: pregnancy; asthma, chronic obstructive pulmonary disease (COPD), bradycardia, heart failure, end-stage renal disease, cerebrovascular accident, diabetes mellitus; preoperative use of nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, or beta-blockers; and body mass index (BMI) greater than 40 kg/m2. Patients received either dose-infused esmolol or intravenous push labetalol. The primary outcome was intraoperative visibility determined by surgeon using validated scoring systems (Boezaart, Wormald). The secondary outcome was hemodynamic control (rate of blood loss, average mean arterial pressure [MAP], average heart rate [HR]). Hypothesis of no difference between drugs formed before data collection. RESULTS: Of the 32 adults given drug (mean age = 50), 28 patients (13 esmolol and 15 labetalol) with complete data were included in the final analysis. There were no statistically significant differences between esmolol and labetalol in rate of blood loss (0.59 [0.28] vs 0.66 [0.37] mL/min, P = 0.62), average MAP (79.7 [7.5] vs 79.4 [7.7] mm Hg, P = .93), HR (72 [8.7] vs 68 [11.7] bpm, P = .26), or mean visibility scores for the Boezaart (3.1 [0.69] vs 3.1 [0.89], P = .85) and Wormald (6.1 [1.7] vs 5.9 [1.9], P = .72) grading scales. CONCLUSIONS: There were no significant differences between esmolol and labetalol in rate of blood loss, MAP control, HR, or surgical visibility in FESS. Either drug may be used, and other considerations (availability, cost) can dictate choice.

Effect of esmolol on fluid therapy in normovolemia and hypovolemia.

beta-Adrenergic agonists can enhance vascular volume expansion after a fluid bolus. The present study addresses how the beta-adrenergic antagonist esmolol influences volume expansion and fluid balance during normovolemia (series 1) and hypovolemia (series 2). Sheep were instrumented, and the spleen was removed. For series 1, continuous infusion of 50 to 100 microg.kg(-1).min(-1) esmolol (n = 6) or control (no drug; n = 6) was begun 30 min before administration of a 24-mL kg(-1) 20-min bolus of 0.9% NaCl. For series 2, anesthetized sheep were infused with 50 to 100 microg.kg(-1).min(-1) esmolol (n = 6) or control (no drug; n = 6) 30 min before a-20 mL kg(-1) hemorrhage. Fluid resuscitation (0.9% NaCl) was begun 30 min after hemorrhage. The 24-mL kg(-1) 20-min bolus was followed by titrated fluid therapy. Hemoglobin, fluid in, and urinary output were used to calculate changes in plasma volume (DeltaPV), extravascular volume (DeltaEVV = fluid in - urinary output - DeltaPV), volume expansion efficiency (VEE = fluid in / DeltaPV), and fluid distribution ratio (DeltaPV/DeltaEVV). Hemodynamics for both series were similar with the exception of heart rate. In series 1, peak DeltaPV was 9.1 +/- 1.0 mL kg(-1) in control and 3.7 +/- 1.0 mL kg(-1) at study end. Esmolol resulted in a lower peak DeltaPV (6.4 +/- 2.0 mL kg(-1)) and a negative DeltaPV (-0.4 +/- 0.6 mL kg(-1)) at study's end. Urinary output was lower, and EVV was greater with esmolol. In series 2, esmolol increased fluid requirements (67 +/- 7 mL kg(-1)) compared with control (54 +/- 5 mL kg(-1)). Esmolol reduced DeltaPV/DeltaEVV. These data suggest that esmolol impairs the vascular retention of fluid and may increase the amount of volume support during fluid resuscitation.

Closed-loop control of fluid therapy for treatment of hypovolemia.

Closed-loop algorithms and resuscitation systems are being developed to control IV infusion rate during early resuscitation of hypovolemia. Although several different physiologic variables have been suggested as an endpoint to guide fluid therapy, blood pressure remains the most used variable for the initial assessment of hemorrhagic shock and the treatment response to volume loading. Closed-loop algorithms use a controller function to alter infusion rate inversely to blood pressure. Studies in hemorrhaged conscious sheep suggest that: (1) a small reduction in target blood pressure can result in a significant reduction in volume requirement; (2) nonlinear algorithms may reduce the risk of increased internal bleeding during resuscitation; (3) algorithm control functions based on proportional-integral, fuzzy logic, or nonlinear decision tables were found to restore and maintain blood pressure equally well. Proportional-integral and fuzzy logic algorithms reduced mean fluid volume requirements compared with the nonlinear decision table; and (4) several algorithms have been constructed to the specific mechanism of injury and the volume expansion properties of different fluids. Closed-loop systems are undergoing translation from animal to patient studies. Future smart resuscitation systems will benefit from new noninvasive technologies for monitoring blood pressure and the development of computer controlled high flow intravenous pumps.

Respiratory Volume Monitoring Reduces Hypoventilation and Apnea in Subjects Undergoing Procedural Sedation.

INTRODUCTION: The use of monitored anesthesia care for endoscopic procedures increases the risk of respiratory depression, necessitating careful monitoring of patient ventilation. We examined the effectiveness of an impedance-based respiratory volume monitor (RVM) in improving the safety of patients undergoing upper and lower gastrointestinal endoscopies under total intravenous anesthesia. We hypothesized that feedback from the RVM would allow anesthesiologists to maintain adequate ventilation, which would reduce the duration of respiratory depression (ie, hypoventilation and apnea) compared to a blinded control group. METHODS: Sixty-five subjects were enrolled in a randomized controlled trial and monitored with a noninvasive impedance-based RVM, which displayed respiratory traces and calculated expiratory minute ventilation (V̇E), tidal volume (VT), and breathing frequency (f) measurements. Prior to induction of anesthesia, a baseline V̇E measurement (V̇E-baseline) was taken as a measurement of normal breathing. V̇E was monitored throughout the procedure for signs of hypoventilation and apnea. Hypoventilation was defined as V̇E < 40% V̇E-baseline, and apneas were defined as V̇E = 0 for > 15 s. RESULTS: Sixty-five subjects were randomly assigned to either a control (n = 38) or RVM intervention group (n = 27). Subjects in the intervention group had a higher V̇E% for the entire procedure (P = .045), as well as the third and fourth quartile of the procedure compared to the control group (P = .01). Likewise, subjects in the RVM intervention group spent significantly less time below 40% V̇E-baseline compared to the control group throughout the entire procedure (12 ± 15% vs 32 ± 24%, respectively) (P < .001). The median number of apneas per subject was greater in the control group (median 2, interquartile range 1-2, maximum 4) compared to the RVM intervention group (median 1, interquartile range 1-2, maximum 3) (P = .037). CONCLUSIONS: The control group had a higher incidence of hypoventilation and apnea compared to the RVM intervention group. Respiratory monitoring using the RVM can potentially be a useful tool for identifying early signs of respiratory depression and for titrating anesthetics to maintain adequate ventilation while minimizing patient risk.

Hypertonic 15% sodium pyruvate offers no initial resuscitation advantage compared with 8% hypertonic NACl in sheep with multiple hemorrhages.

Initial fluid resuscitation of hemorrhagic shock might be enhanced by the infusion of monocarboxylate-energy substrates. We evaluated hemodynamics, metabolism, and fluid dynamics for initial resuscitation of hemorrhage using small volume 15% sodium pyruvate solution (HPY) compared with osmotically matched 8% hypertonic saline (HS). Instrumented conscious sheep were hemorrhaged 25 mL/kg at time zero through 15 min (T0-T15) and 5 mL/kg for 5 min at T50 to T55 and T70 to T75. Fluid resuscitation from T30 to T180 was performed by a computer-controlled closed-loop system, which titrated infusion rate to a mean arterial pressure of 90 mmHg. Initial infusion was 4 mL/kg of either HPY or HS, followed by the administration of lactated Ringer. Both HPY and HS restored cardiac index similarly. The lactate/pyruvate ratio was used to assess metabolic debt and was significantly higher (T180), whereas oxygen delivery was significantly lower (T120) with HPY versus HS. Total fluid administered was similar, with 43.7 +/- 6.2 mL/kg for HPY and 39.4 +/- 6.8 mL/kg for HS. Plasma volume was similarly increased and approached baseline values for both groups. Initial resuscitation with small volume HPY offered no hemodynamic or metabolic advantage compared with small volume HS when the fluids were infused to an end point pressure.

Closed-Loop Control of FiO2 Rapidly Identifies Need For Rescue Ventilation and Reduces ARDS Severity in a Conscious Sheep Model of Burn and Smoke Inhalation Injury.

Pulmonary injury can be characterized by an increased need for fraction of inspired oxygen or inspired oxygen percentage (FiO2) to maintain arterial blood saturation of oxygenation (SaO2). We tested a smart oxygenation system (SOS) that uses the activity of a closed-loop control FiO2 algorithm (CLC-FiO2) to rapidly assess acute respiratory distress syndrome (ARDS) severity so that rescue ventilation (RscVent) can be initiated earlier. After baseline data, a pulse-oximeter (noninvasive saturation of peripheral oxygenation [SpO2]) was placed. Sheep were then subjected to burn and smoke inhalation injury and followed for 48 h. Initially, sheep were spontaneously ventilating and then randomized to standard of care (SOC) (n = 6), in which RscVent began when partial pressure of oxygen (PaO2) < 90 mmHg or FiO2 < 0.6, versus SOS (n = 7), software that incorporates and displays SpO2, CLC-FiO2, and SpO2/CLC-FiO2 ratio, at which RscVent was initiated when ratio threshold < 250. RscVent was achieved using a G5 Hamilton ventilator (Bonaduz, Switzerland) with adaptive pressure ventilation and adaptive support ventilation modes for SOC and SOS, respectively. OUTCOMES: the time difference from when SpO2/FiO2 < 250 to RscVent initiation was 4.7 ±â€Š0.6 h and 0.2 ±â€Š0.1 h, SOC and SOS, respectively (P < 0.001). Oxygen responsiveness after RscVent, defined as SpO2/FiO2 > 250 occurred in 4/7, SOS and 0/7, SOC. At 48 h the SpO2/FiO2 ratio was 104 ±â€Š5 in SOC versus 228 ±â€Š59 in SOS (P = 0.036). Ventilatory compliance and peak airway pressures were significantly improved with SOS versus SOC (P < 0.001). Data suggest that SOS software, e.g. SpO2/CLC-FiO2 ratio, after experimental ARDS can provide a novel continuous index of pulmonary function that is apparent before other clinical symptoms. Earlier initiation of RscVent translates into improved oxygenation (reduces ARDS severity) and ventilation.

Long-term effect of critical illness after severe paediatric burn injury on cardiac function in adolescent survivors: an observational study.

BACKGROUND: Sepsis, trauma, and burn injury acutely depress systolic and diastolic cardiac function; data on long-term cardiac sequelae of pediatric critical illness are sparse. This study evaluated long-term systolic and diastolic function, myocardial fibrosis, and exercise tolerance in survivors of severe pediatric burn injury. METHODS: Subjects at least 5 years after severe burn (post-burn:PB) and age-matched healthy controls (HC) underwent echocardiography to quantify systolic function (ejection fraction[EF%]), diastolic function (E/e'), and myocardial fibrosis (calibrated integrated backscatter) of the left ventricle. Exercise tolerance was quantified by oxygen consumption (VO2) and heart rate at rest and peak exercise. Demographic information, clinical data, and biomarker expression were used to predict long-term cardiac dysfunction and fibrosis. FINDINGS: Sixty-five subjects (PB:40;HC:25) were evaluated. At study date, PB subjects were 19±5 years, were at 12±4 years postburn, and had burns over 59±19% of total body surface area, sustained at 8±5 years of age. The PB group had lower EF% (PB:52±9%;HC:61±6%; p=0.004), E/e' (PB:9.8±2.9;HC: 5.4±0.9;p<0.0001), VO2peak (PB:37.9±12;HC: 46±8.32 ml/min/kg; p=0.029), and peak heart rate (PB:161±26;HC:182±13bpm;p=0.007). The PB group had moderate (28%) or severe (15%) systolic dysfunction, moderate (50%) or severe diastolic dysfunction (21%), and myocardial fibrosis (18%). Biomarkers and clinical parameters predicted myocardial fibrosis, systolic dysfunction, and diastolic dysfunction. INTERPRETATION: Severe pediatric burn injury may have lasting impact on cardiac function into young adulthood and is associated with myocardial fibrosis and reduced exercise tolerance. Given the strong predictive value of systolic and diastolic dysfunction, these patients might be at increased risk for early heart failure, associated morbidity, and mortality. FUNDING: Conflicts of Interest and Sources of Funding: The authors do not have any conflicts of interest to declare. This work was supported by NIH (P50 GM060338, R01 GM056687, R01 HD049471, R01 GM112936, R01-GM56687 and T32 GM008256), NIDILRR (H133A120091, 90DP00430100), Shriners Hospitals for Children (84080, 79141, 79135, 71009, 80100, 71008, 87300 and 71000), FAER (MRTG CON14876), and the Department of Defense (W81XWH-14-2-0162 and W81XWH1420162). It was also made possible with the support of UTMB's Institute for Translational Sciences, supported in part by a Clinical and Translational Science Award (UL1TR000071) from the National Center for Advancing Translational Sciences (NIH).