Dynamic and volumetric variables reliably predict fluid responsiveness in a porcine model with pleural effusion

Background: The ability of stroke volume variation (SVV), pulse pressure variation (PPV) and global end-diastolic volume (GEDV) for prediction of fluid responsiveness in presence of pleural effusion is unknown. The aim of the present study was to challenge the ability of SVV, PPV and GEDV to predict fluid responsiveness in a porcine model with pleural effusions. Methods: Pigs were studied at baseline and after fluid loading with 8 ml kg−1 6% hydroxyethyl starch. After withdrawal of 8 ml kg−1 blood and induction of pleural effusion up to 50 ml kg−1 on either side, measurements at baseline and after fluid loading were repeated. Cardiac output, stroke volume, central venous pressure (CVP) and pulmonary occlusion pressure (PAOP) were obtained by pulmonary thermodilution, whereas GEDV was determined by transpulmonary thermodilution. SVV and PPV were monitored continuously by pulse contour analysis. Results: Pleural effusion was associated with significant changes in lung compliance, peak airway pressure and stroke volume in both responders and non-responders. At baseline, SVV, PPV and GEDV reliably predicted fluid responsiveness (area under the curve 0.85 (p<0.001), 0.88 (p<0.001), 0.77 (p = 0.007). After induction of pleural effusion the ability of SVV, PPV and GEDV to predict fluid responsiveness was well preserved and also PAOP was predictive. Threshold values for SVV and PPV increased in presence of pleural effusion. Conclusions: In this porcine model, bilateral pleural effusion did not affect the ability of SVV, PPV and GEDV to predict fluid responsiveness

Perioperative fluid administration to optimise haemodynamics without fluid overload in anaesthetised dogs : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterinary Science at Massey University, Manawatu, New Zealand

Perioperative fluid therapy is the mainstay of anaesthetic management. Fluid administration improves haemodynamics during anaesthesia as it increases preload and thus cardiac output and blood pressure. However, excessive fluid administration can cause detrimental adverse effects, such as haemodulution and oedema, resulting in prolonged hospital stay and increased morbidity and mortality in people. Therefore, fluid administration should be restricted to those who are able to increase stroke volume or cardiac output in response to the fluid administration (responders) and should not be given to those who are unable to do so (non-responders) based on the famous “Frank–Starling law of the heart” Previously static parameters such as central venous pressure were believed to be a clinical gold standard to estimate preload and fluid responsiveness. Over the last decade, dynamic parameters such as pulse pressure variation and pleth variability index have been shown to be reliable predictors for fluid responsiveness in people. This study found that pulse pressure variation and pleth variability index were more accurate than central venous pressure for predicting fluid responsiveness in dogs. Mini-fluid challenge is another technique that is currently available and can be reliably used to determine fluid responsiveness in human medicine. Mini-fluid challenge is an administration of a small amount of fluid to increase preload. Thus, fluid responsiveness can be assessed based on whether stroke volume increases following mini-fluid challenge according to the Frank-Starling curve. The change in stroke volume of a heart at the steep portion of the Frank-Starling curve will be greater than at the plateau portion after mini-fluid challenge. The studies revealed a percentage change in pulse wave transit time (a surrogate parameter of stroke volume, which was also one of results in this thesis) following mini-fluid challenge could predict fluid responsiveness in mechanically ventilated anaesthetised dogs under an experimental condition, and spontaneously breathing anaesthetised dogs undergoing stifle surgery in clinical setting. Lastly, these methods are still of limited use in veterinary clinical practice because of availability of equipment, difficulty of their interpretation and a cumbersome process. The main purpose of this thesis was to obtain evidence on how to optimise haemodynamics in anaesthetised dogs and prevent excessive fluid administration. The time when most practitioners administer a bolus of fluid during anaesthesia is when hypotension is encountered because of anaesthesia. Thus, prevention of hypotension could avoid excessive fluid administration. Therefore, the study found that prophylactic noradrenaline administration, which counteracts some of the cardiovascular adverse effects of anaesthesia, was able to prevent hypotension, and thus minimise fluid administration in anaesthetised dogs. Although all of these methods tested in this thesis have pros and cons in clinical veterinary practice, they were shown to be able to optimise haemodynamics without fluid overload in anaesthetised dogs

Duration of hemodynamic effects of crystalloids in patients with circulatory shock after initial resuscitation

Background: in the later stages of circulatory shock, monitoring should help to avoid fluid overload. in this setting, volume expansion is ideally indicated only for patients in whom the cardiac index (CI) is expected to increase. Crystalloids are usually the choice for fluid replacement. As previous studies evaluating the hemodynamic effect of crystalloids have not distinguished responders from non-responders, the present study was designed to evaluate the duration of the hemodynamic effects of crystalloids according to the fluid responsiveness status.Methods: This is a prospective observational study conducted after the initial resuscitation phase of circulatory shock (>6 h vasopressor use). Critically ill, sedated adult patients monitored with a pulmonary artery catheter who received a fluid challenge with crystalloids (500 mL infused over 30 min) were included. Hemodynamic variables were measured at baseline (T0) and at 30 min (T1), 60 min (T2), and 90 min (T3) after a fluid bolus, totaling 90 min of observation. the patients were analyzed according to their fluid responsiveness status (responders with CI increase >15% and non-responders <= 15% at T1). the data were analyzed by repeated measures of analysis of variance.Results: Twenty patients were included, 14 of whom had septic shock. Overall, volume expansion significantly increased the CI: 3.03 +/- 0.64 L/min/m(2) to 3.58 +/- 0.66 L/min/m(2) (p < 0.05). From this period, there was a progressive decrease: 3.23 +/- 0.65 L/min/m(2) (p < 0.05, T2 versus T1) and 3.12 +/- 0.64 L/min/m(2) (p < 0.05, period T3 versus T1). Similar behavior was observed in responders (13 patients), 2.84 +/- 0.61 L/min/m(2) to 3.57 +/- 0.65 L/min/m(2) (p < 0.05) with volume expansion, followed by a decrease, 3.19 +/- 0.69 L/min/m(2) (p < 0.05, T2 versus T1) and 3.06 +/- 0.70 L/min/m(2) (p < 0.05, T3 versus T1). Blood pressure and cardiac filling pressures also decreased significantly after T1 with similar findings in both responders and non-responders.Conclusions: the results suggest that volume expansion with crystalloids in patients with circulatory shock after the initial resuscitation has limited success, even in responders.Universidade Federal de São Paulo, Disciplina Anestesiol Dor & Terapia Intens, BR-04024900 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Anestesiol Dor & Terapia Intens, BR-04024900 São Paulo, BrazilWeb of Scienc

Cell-Free DNA and CXCL10 Derived from Bronchoalveolar Lavage Predict Lung Transplant Survival.

Standard methods for detecting chronic lung allograft dysfunction (CLAD) and rejection have poor sensitivity and specificity and have conventionally required bronchoscopies and biopsies. Plasma cell-free DNA (cfDNA) has been shown to be increased in various types of allograft injury in transplant recipients and CXCL10 has been reported to be increased in the lung tissue of patients undergoing CLAD. This study used a novel cfDNA and CXCL10 assay to evaluate the noninvasive assessment of CLAD phenotype and prediction of survival from bronchoalveolar lavage (BAL) fluid. A total of 60 BAL samples (20 with bronchiolitis obliterans (BOS), 20 with restrictive allograft syndrome (RAS), and 20 with stable allografts (STA)) were collected from 60 unique lung transplant patients; cfDNA and CXCL10 were measured by the ELISA-based KIT assay. Median cfDNA was significantly higher in BOS patients (6739 genomic equivalents (GE)/mL) versus STA (2920 GE/mL) and RAS (4174 GE/mL) (p &lt; 0.01 all comparisons). Likelihood ratio tests revealed a significant association of overall survival with cfDNA (p = 0.0083), CXCL10 (p = 0.0146), and the interaction of cfDNA and CXCL10 (p = 0.023) based on multivariate Cox proportional hazards regression. Dichotomizing patients based on the median cfDNA level controlled for the mean level of CXCL10 revealed an over two-fold longer median overall survival time in patients with low levels of cfDNA. The KIT assay could predict allograft survival with superior performance compared with traditional biomarkers. These data support the pursuit of larger prospective studies to evaluate the predictive performance of cfDNA and CXCL10 prior to lung allograft failure

Thyroxine-binding globulin: investigation of microheterogeneity

Preparations of T4-binding globulin (TBG) from human serum was performed using only two affinity chromatography steps. Purity of the protein was demonstrated by a single band in overloaded disc and sodium dodecyl sulfate electrophoresis, equimolar binding to T4, and linearity in sedimentation velocity run. The molecular weight was calculated to be 60,000 +/- 3,000 daltons (n = 3), the sedimentation coefficient was 3.95S, and the Stokes' radius was 37 A. The amino acid composition was found to be in good agreement with the calculations of other authors. By isoelectric focussing (IEF), pure TBG showed four main bands at pH 4.25, 4.35, 4.45, and 4.55 together with several fainter bands. The N- acetylneuraminic acid (NANA) content of the four TBG bands isolated by preparative IEF was found to decrease from 10.2 mol NANA/mol TBG in the band at pH 4.25 to 4.8 mol NANA/mol TBG in the band at pH 4.55. No significant difference in the affinity constants of the TBG bands to T4 was found. The affinity constants for TBG ranged from 3.1 x 10(9) to 7.2 x 10(9) M-1. Sequential kinetic desialylation of pure TBG resulted in a progressive tendency toward one major band at pH 6.0. In native sera, microheterogeneity of TBG was detected after IEF on polyacrylamide gel plates by immunofixation. The typical TBG patterns shown by pure TBG were also found in normal subjects. Characteristic deviations from this pattern were found in the sera of females during estrogen therapy or pregnancy, where there was a gradual increase in density of the band at pH 4.25 and the appearance of an additional band at pH 4.15. In sera from patients with liver disease and elevated TBG levels, there was a fading of the acidic bands, whereas the more alkaline band at pH 4.55 was intensified. It is therefore proposed that microheterogeneity of TBG is caused by differences in NANA content and that variations of TBG patterns in native sera may reflect altered TBG synthesis or degradation. A genetically related microheterogeneity of TBG could not be demonstrated after examination of 800 sera, including 2 families with quantitative TBG deficiency

American Society for Enhanced Recovery (ASER) and Perioperative Quality Initiative (POQI) joint consensus statement on perioperative fluid management within an enhanced recovery pathway for colorectal surgery

BACKGROUND: Enhanced recovery may be viewed as a comprehensive approach to improving meaningful outcomes in patients undergoing major surgery. Evidence to support enhanced recovery pathways (ERPs) is strong in patients undergoing colorectal surgery. There is some controversy about the adoption of specific elements in enhanced recovery "bundles" because the relative importance of different components of ERPs is hard to discern (a consequence of multiple simultaneous changes in clinical practice when ERPs are initiated). There is evidence that specific approaches to fluid management are better than alternatives in patients undergoing colorectal surgery; however, several specific questions remain. METHODS: In the "Perioperative Quality Initiative (POQI) Fluids" workgroup, we developed a framework broadly applicable to the perioperative management of intravenous fluid therapy in patients undergoing elective colorectal surgery within an ERP. DISCUSSION: We discussed aspects of ERPs that impact fluid management and made recommendations or suggestions on topics such as bowel preparation; preoperative oral hydration; intraoperative fluid therapy with and without devices for goal-directed fluid therapy; and type of fluid

Small-volume resuscitation with hyperoncotic albumin: a systematic review of randomized clinical trials

Background Small-volume resuscitation can rapidly correct hypovolemia. Hyperoncotic albumin solutions, long in clinical use, are suitable for small-volume resuscitation; however, their clinical benefits remain uncertain. Methods Randomized clinical trials comparing hyperoncotic albumin with a control regimen for volume expansion were sought by multiple methods, including computer searches of bibliographic databases, perusal of reference lists, and manual searching. Major findings were qualitatively summarized. In addition, a quantitative meta-analysis was performed on available survival data. Results In all, 25 randomized clinical trials with a total of 1,485 patients were included. In surgery, hyperoncotic albumin preserved renal function and reduced intestinal edema compared with control fluids. In trauma and sepsis, cardiac index and oxygenation were higher after administration of hydroxyethyl starch than hyperoncotic albumin. Improved treatment response and renal function, shorter hospital stay and lower costs of care were reported in patients with liver disease receiving hyperoncotic albumin. Edema and morbidity were decreased in high-risk neonates after hyperoncotic albumin administration. Disability was reduced by therapy with hyperoncotic albumin in brain injury. There was no evidence of deleterious effects attributable to hyperoncotic albumin. Survival was unaffected by hyperoncotic albumin (pooled relative risk, 0.95; 95% confidence interval 0.78 to 1.17). Conclusion In some clinical indications, randomized trial evidence has suggested certain benefits of hyperoncotic albumin such as reductions in morbidity, renal impairment and edema. However, further clinical trials are needed, particularly in surgery, trauma and sepsis

Plethysmography Variation Index (PVI) Utility In Guiding Goal-Directed Fluid Therapy During Major Abdominal Surgery

When considering intra-operative MAP maintenance, preload is a significant driving factor of stroke volume and therefore cardiac output. In major abdominal surgeries, large fluid shifts are common and accurate fluid resuscitation is extremely important to maintain hemodynamic stability and promote optimal patient outcomes. Invasive methods of measuring fluid status range from esophageal doppler derived flow time (FTc) and arterial line-derived metrics such as stroke volume variation (SVV) and pulse pressure variation (PPV). However, invasive means are not always warranted for every surgical procedure or patient and there is a higher potential risk for complication. Plethysmography Variation Index (PVI) has been introduced as a non-invasive alternative to gauge preload status, predict fluid responsiveness, and guide goal-directed fluid therapy. The success of PVI during major abdominal surgery is mixed. Significant predictive ability to determine fluid responsiveness exists and compares well to invasive techniques. However, the ability to track dynamic stroke volume (SV) changes correlates poorly with fluid bolus administration and PVI tracings. Overall, the total volume of fluid administered and post-operative patient outcomes all compare favorably with PPV, SVV, and FTc. Ultimately, the use of PVI during major abdominal surgery can be useful if fluid management is considered and approached in at least two distinct parts: first, recognition of hypovolemia and fluid responsiveness, to which PVI can accurately provide data; second, continued tracking of hemodynamic changes post bolus and the warranting of subsequent boluses, to which PVI is not well suited to direct

Optimal Counseling And The Utility Of Imaging Parameters In Patients With Idiopathic Normal Pressure Hydrocephalus

It is very difficult to counsel patients who are suspected to have idiopathic normal pressure hydrocephalus (iNPH) due to the variability in diagnostic criteria and clinical presentations, as well as the difficulty in evaluating prognosis. This two part study was conducted in order to identify ways to improve the counseling of patients with iNPH. A qualitative analysis of patient experience with iNPH and shunting was initially performed. This was followed by an imaging analysis to identify predictors of outcome after shunt surgery. A cohort of patients with iNPH who were shunted at a single institution were identified retrospectively and interviewed to explore patient experience. Interview transcripts were analyzed using the principles of grounded theory, which yielded seven overarching themes. From these themes, it was concluded that patients: suffer from a long preoperative course, desire improvement in functional independence, are not affected by the inability to provide a prognosis associated with shunt surgery, are confounded by comorbid conditions, and receive heavy influence from family members and caregivers. These conclusions can be incorporated by physicians to improve patient counseling. Features on the brain imaging of the same cohort of patients were reviewed retrospectively and compared with patient-reported subjective binary outcomes obtained from the patient interviews. A few imaging features were found to be possible predictors of outcome after shunting. The presence of focally dilated sulci may be a predictor of gait improvement, and a larger Evans\u27 index, larger third ventricular diameter, and larger callosal height, may all be predictors of cognitive improvement. However, there is significant discordance in the literature regarding the predictive value of imaging features. The utility of imaging parameters in patient counseling remains limited until more consistent results can be produced