Pathogenetic therapy of vascular-platelet hemostasis disorders in canine acute spontaneous babesiosis

The article presents the results of a study of the vascular-platelet hemostasis disorders processes in complications of canine acute spontaneous babesiosis, as well as a clinical trial of plasma substitute infusion for the purpose of identified disorders pathogenetic therapy. It was found that acute spontaneous Babesiosis is accompanied by complications in the form of subcompensated shock and a thrombogenic link of disseminated intravascular coagulation syndrome (DIC). This determines the potential risk of complications with a cautious prognosis. The basis for the diagnosis of complications is the establishment of the following changes: a significant deficit in the volume of circulating blood (a decrease in the hematocrit value, the volume of circulating plasma, the volume of circulating red blood cells, the specific volume of circulating blood), as well as significant changes in the functioning of the vascular-platelet link of hemostasis – thrombocytopenia against the background of an increase in the spontaneous aggregation ability of platelets and red blood cells, an increase in the wetting index of the vascular wall, which determines the thrombogenic state, and pronounced thrombocytopenia indicates the consumption of these shaped elements in blood clots. The described changes indicate the development of subcompensated shock and the thrombogenic component of DIC syndrome. Given the prognostic danger of established complications, there is a need for pathogenetic therapy of severe conditions. Infusions of plasma substitute solutions have been proposed to eliminate shock phenomena and the thrombogenic state of disseminated intravascular coagulation syndrome. A clinical trial of intravenous administration of Rheosorbylact solution and a mixture of Rheosorbylact with Dipyridamole was conducted in a comparative aspect. It is shown that a mixture of Rheosorbylact 100 ml and Dipyridamole solution 0.5 % 4 ml in the form of infusions at a dose of 5 ml/kg of animal body weight per day for 3 days can bring hemodynamic parameters and parameters of vascular-platelet hemostasis to physiological ones within 48 hours compared to an infusion of Rheosorbylact solution in its pure form. The synergy of the crystalloid solution of Rheosorbylact and the disaggregating vasodilator Dipyridamole enhances the disaggregating effect of both drugs, and the crystalloid solution itself is able to restore the lost volume of circulating blood.

Cardioplegia between Evolution and Revolution: From Depolarized to Polarized Cardiac Arrest in Adult Cardiac Surgery

Despite current advances in perioperative care, intraoperative myocardial protection during cardiac surgery has not kept the same pace. High potassium cardioplegic solutions were introduced in the 1950s, and in the early 1960s they were soon recognized as harmful. Since that time, surgeons have minimized many of the adverse effects by lowering the temperature of the heart, lowering K+ concentration, reducing contact K+ time, changing the vehicle from a crystalloid solution to whole-blood, adding many pharmacological protectants and modifying reperfusion conditions. Despite these attempts, high potassium remains a suboptimalway to arrest the heart. We briefly review the historical advances and failures of finding alternatives to high potassium, the drawbacks of a prolonged depolarized membrane, altered Ca2+ intracellular circuits and heterogeneity in atrial-ventricular K+ repolarization during reanimation. Many of these untoward effects may be alleviated by a polarized membrane, and we will discuss the basic science and clinical experience from a number of institutions trialling different alternatives, and our institution with a non-depolarizing adenosine, lidocaine and magnesium (ALM) cardioplegia. The future of polarized arrest is an exciting one and may play an important role in treating the next generation of patients who are older, and sicker with multiple comorbidities and require more complex operations with prolonged cross-clamping times.

Albumin Oxidation Status in Sepsis Patients Treated With Albumin or Crystalloids

Inflammation and oxidative stress characterize sepsis and determine its severity. In this study, we investigated the relationship between albumin oxidation and sepsis severity in a selected cohort of patients from the Albumin Italian Outcome Study (ALBIOS). A retrospective analysis was conducted on the oxidation forms of human albumin [human mercapto-albumin (HMA), human non-mercapto-albumin form 1 (HNA1) and human non-mercapto-albumin form 2 (HNA2)] in 60 patients with severe sepsis or septic shock and 21 healthy controls. The sepsis patients were randomized (1:1) to treatment with 20% albumin and crystalloid solution or crystalloid solution alone. The albumin oxidation forms were measured at day 1 and day 7. To assess the albumin oxidation forms as a function of oxidative stress, the 60 sepsis patients, regardless of the treatment, were grouped based on baseline sequential organ failure assessment (SOFA) score as surrogate marker of oxidative stress. At day 1, septic patients had significantly lower levels of HMA and higher levels of HNA1 and HNA2 than healthy controls. HMA and HNA1 concentrations were similar in patients treated with albumin or crystalloids at day 1, while HNA2 concentration was significantly greater in albumin-treated patients (p < 0.001). On day 7, HMA was significantly higher in albumin-treated patients, while HNA2 significantly increased only in the crystalloids-treated group, reaching values comparable with the albumin group. When pooling the septic patients regardless of treatment, albumin oxidation was similar across all SOFA groups at day 1, but at day 7 HMA was lower at higher SOFA scores. Mortality rate was independently associated with albumin oxidation levels measured at day 7 (HMA log-rank = 0.027 and HNA2 log-rank = 0.002), irrespective of treatment group. In adjusted regression analyses for 90-day mortality, this effect remained significant for HMA and HNA2. Our data suggest that the oxidation status of albumin is modified according to the time of exposure to oxidative stress (differences between day 1 and day 7). After 7 days of treatment, lower SOFA scores correlate with higher albumin antioxidant capacity. The trend toward a positive effect of albumin treatment, while not statistically significant, warrants further investigation.

The influence of solution choice on fluid resuscitation in patients with septic shock

The aim. Compare the hemodynamic effects and safety of infusion of the balanced crystalloid solution, sorbitol-based solution, and standard solution (0.9 % sodium chloride). Materials and methods. A prospective randomized clinical trial was carried out, the study included 68 adult patients, who had the active surgical infection, and were in a state of septic shock. A corresponding solution with a volume of 500 ml was used for resuscitation. Hemodynamic and other clinical and laboratory parameters were monitored. Results. There was no significant difference in mean arterial pressure (MAP) between the 3 groups before the 45th minute (p>0.05), from the 50th minute to 2 hours they were found only between the NS and Sorb groups (p <0.05). No statistically significant difference in heart rate (HR) was obtained in any measurement (p> 0.05). Cardiac output (CO) and oxygen delivery (DO2) did not differ until 35 min (p> 0.05) and up to 40 min (p> 0.05); after 40 min and 45 min, a significant difference was also found between the Sorb and NS groups (p <0.05). After infusion of a sorbitol-containing solution and a balanced polyionic solution, the acid-base state of the blood significantly improved. The applied dose of the sorbitol-containing solution was safe for renal function and blood clotting in septic shock in this study. But the applied balanced polyionic solution may be associated with a decrease in the number of platelets. Daily changes by APACHE II scores in each group were not statistically significant. The difference in 7-day and 28-day mortality between groups was not statistically significant (p>0.05). Conclusions. In our study, the balanced polyionic solution with 1.9 % sodium lactate and 6 % sorbitol was the most effective and safe infusion solution for the treatment of septic shock, it can be used as a supplement to balanced crystalloid solutions. When using a balanced polyionic solution (Ringer's acetate) with 0.07 % L-malonic acid, the platelet count should be monitored more often

Efficacy of Intravenous Fluid Plasmalyte and 6% Hetastarch in Preventing Spinal Anaesthesia Induced Hypotension in Patients undergoing Lower Abdominal Surgeries: A Randomised Clinical Study

Introduction: Both crystalloids and colloid preloading is recommended for spinal anaesthesia. Preloading of intravenous fluids increases circulating volume and cardiac output; thus preventing spinal anaesthesia-induced hypotension. Crystalloids have a short intravascular half-life, poor plasma expanders and large volumes are thus required. Aim: To compare the efficacy of 5 mL/kg of 6% Hetastarch (colloid) to that of 15 mL/kg of Plasmalyte (crystalloid) solution to prevent hypotension during spinal anaesthesia in patients undergoing lower abdominal surgeries. Materials and Methods: This was a randomised clinical trial from June 2016 to April 2017 on a total 80 patients, belonging to American Society of Anaesthesiologist (ASA) Grade I and II scheduled for lower abdominal surgeries under spinal anaesthesia. They were divided into two groups- Group H and Group P. Patients in group H were preloaded with 5 mL/kg solution of 6% Hetastarch, whereas those in group P were preloaded with 15 mL/kg of Plasmalyte solution. After institution of spinal anaesthesia with 3.0 mL of hyperbaric Bupivacaine using 25G Quincke’s needle, Blood Pressure (BP) and other vital parameters were monitored intraoperatively every 3 minutes for first 30 minutes and then every 5 minutes till the end of surgery. Descriptive statistics, frequency (n) and percentages (%) were calculated and the variables between the groups were compared by Students t-test, Fischers exact test and Mann Whitney U-test. Results: Both the groups showed a fall in Mean Blood Pressure (MBP) immediately after the block. Group P showed more decline in MBP and Diastolic Blood Pressure (DBP) after the block and thedifference was statistically significant at 9, 12, 15, 18 and 21minute (p-value <0.05). A 30% patients in group P as comparison to 10% in Group H required ephedrine for the treatment of hypotension and found significant (p-value=0.025). Systolic Blood Pressure (SBP), pulse rate changes and nausea and vomiting among both groups was non-significant (p-value >0.05). Conclusion: Pre-loading with 5ml/kg of 6% Hetastarch is more effective than 15ml/kg of Plasmalyte in preventing hypotension in patients undergoing lower abdominal surgeries under spinal anaesthesia.

Investigation of myocardial protection during pediatric CPB: Practical experience in 100 Chinese hospitals

Many measures have been proposed for myocardial protection in pediatric congenital heart surgeries, but little data is available for China. This study investigates myocardial protection strategies in pediatric cardiopulmonary bypass (CPB) throughout China. Online questionnaires were delivered to 100 hospitals in 27 provinces. The number of yearly on-pump pediatric cardiovascular surgeries in these hospitals varied greatly. About 91.0% of respondents believe that each surgery should have at least two perfusionists, while only 64.0% of hospitals actually met this requirement. For pediatric patients, crystalloid cardioplegia was more prevalent than blood-based cardioplegia. Histidine-tryptophan-ketoglutarate solution and St. Thomas crystalloid solution were dominant among crystalloid cardioplegia. Del Nido cardioplegia and St. Thomas blood-based cardioplegia ranked the top two in the popularity of blood-based cardioplegia. Dosages varied among different kinds of cardioplegia. In the choice of different cardioplegia, perfusionists mainly focused on myocardial protective effect and cost. Hypothermia of cardioplegia solution was maintained by ice buckets in 3/4 of the hospitals in this survey. In conclusion, the essence of myocardial protection management during pediatric CPB was cardiac arrest induced by cardioplegia under systemic hypothermia. However, there is no uniform standard for the type of cardioplegia, or dosages. Therefore, well-designed multicenter randomized controlled trials are warranted to provide tangible evidence for myocardial protection of cardioplegia in pediatric CPB.

Sufficient Thrombin Generation Despite 95% Hemodilution: An In Vitro Experimental Study

Guidelines for the treatment of severe bleeding comprise viscoelastic-test-guided use of coagulation factor concentrates as part of their recommendations. The aim of this study is to investigate the effects of substituting fibrinogen, prothrombin complex concentrate, and a combination of both on conventional coagulation tests, viscoelastic test results, and thrombin generation. Blood was drawn from seven healthy volunteers to obtain platelet-free plasma, which later was diluted by replacing 40%, 60%, 80%, 90%, 95%, and 99% with a crystalloid solution. The diluted samples were spiked with fibrinogen concentrate, prothrombin complex concentrate, a combination of both, or a corresponding amount of crystalloid solution. Up to a dilution level of 95%, viscoelastically determined clotting time was significantly shorter in the group substituted with fibrinogen only in comparison with the additional use of prothrombin complex concentrate. Clot firmness and endogenous thrombin potential remained at relatively stable values up to a dilution level of 95% with the substitution of fibrinogen but not prothrombin complex concentrate. Substitution of prothrombin complex concentrate led to an excessive overshoot of thrombin generation. The results of our study question currently propagated treatment algorithms for bleeding patients that include the use of prothrombin complex concentrate for patients without former intake of oral anticoagulants. Even in severely bleeding patients, thrombin generation might be sufficient to achieve adequate hemostasis.

Statistical Analysis Plan for the Plasma-Lyte 148® versUs Saline Study (PLUS) trial

PLUS study is a prospective, multi-centre, parallel group, concealed, blinded, randomised, controlled trial to determine whether fluid resuscitation and therapy with a “balanced” crystalloid solution (Plasma-Lyte 148®) decreases 90-day mortality in critically ill patients requiring fluid resuscitation when compared with the same treatment using 0.9% sodium chloride (saline). This detailed statistical analysis plan (SAP) was written by the trial statistician, chief investigator and project manager and approved by the PLUS management committee prior to unblinding and completion of data collection.

Myocardial protection in cardiac surgery: how limited are the options? A comprehensive literature review

For patients undergoing cardiopulmonary bypass, myocardial protection is a key for successful recovery and improved outcomes following cardiac surgery that requires cardiac arrest. Different solutions, components and modes of delivery have evolved over the last few decades to optimise myocardial protection. These include cold and warm and blood and crystalloid solution through antegrade, retrograde or combined cardioplegia delivery approach. However, each method has its own advantages and disadvantages, posing a challenge to establish a gold-standard cardioplegic solution with an optimised mode of delivery for enhanced myocardial protection during cardiac surgery. The aim of this review is to provide a brief history of the development of cardioplegia, explain the electrophysiological concepts behind myocardial protection in cardioplegia, analyse the current literature and summarise existing evidence that warrants the use of varying cardioplegic techniques. We provide a comprehensive and comparative overview of the effectiveness of each technique in achieving optimal cardioprotection and propose novel techniques for optimising myocardial protection in the future.