What is the best treatment for hypotension in healthy dogs during anaesthesia maintained with isoflurane?

Hypotension is a common and potentially life-threatening complication of general anaesthesia in dogs. Due to the combination of cardiovascular side effects of many anaesthetic, sedative and analgesic drugs used peri-operatively hypotension is frequently reported even in healthy dogs undergoing elective procedures. Several treatment options for hypotension have been advocated. Potential treatments include rapid administration of either crystalloid or colloid fluids; pharmacological treatments to increase cardiac output and/or systemic vascular resistance; or reduction in the delivery of the volatile anaesthetic agents. This critical appraisal considers the current evidence for which treatment is the best option for treating hypotension in healthy euvolemic dogs undergoing general anaesthesia maintained with isoflurane. Fourteen relevant studies were appraised, including 12 laboratory studies and two small clinical trials. One study demonstrated that reduction in the delivery of isoflurane may correct hypotension, but this treatment may not always be feasible. In general, rapid administration of fluids did not increase blood pressure and failed to correct hypotension. Synthetic colloids demonstrated some efficacy, but results were inconsistent between studies and large volumes may be required. Infusion of dopamine appears to be the most reliable pharmacological option consistently increasing blood pressure, cardiac output and correcting hypotension.

Assessing resuscitation in burn patients with varying degrees of liver disease.

We find minimal literature and lack of consensus among burn practitioners over how to resuscitate thermally injured patients with pre-existing liver disease. Our objective was to assess burn severity in patients with a previous history of liver disease. We attempted to stratify resuscitation therapy utilised, using it as an indicator of burn shock severity. We hypothesized that as severity of liver disease increased, more fluid therapy is needed. We retrospectively studied adult patients with a total body surface area (TBSA) of burn greater than or equal to 20% (n = 314). We determined the severity of liver disease by calculating admission Model for End-Stage Liver Disease (MELD) scores and measured resuscitation adequacy via urine output within the first 24 h. We performed stepwise, multivariable linear regression with backward selection to test our hypothesis with α = 0.05 defined a priori. After controlling for important confounders including age, TBSA, baseline serum albumin, total crystalloids, colloids, blood products, diuretics, and steroids given in first 24 h, we found a statistically significant reduction in urine output as MELD score increased (p < 0.000). In our study, severity of liver disease correlated with declining urine output during first 24-hour resuscitation more so than burn size or burn depth. While resuscitation is standardized for all patients, lack of urine output with increased liver disease suggests a new strategy is of benefit. This may involve investigation of alternate markers of adequacy of resuscitation, or developing modified resuscitation protocols for use in patients with liver disease. More investigation is necessary into how resuscitation protocols may best be modified.

Goal-directed colloid versus crystalloid therapy and microcirculatory blood flow following ischemia/reperfusion.

OBJECTIVE: Ischemia/reperfusion can impair microcirculatory blood flow. It remains unknown whether colloids are superior to crystalloids for restoration of microcirculatory blood flow during ischemia/reperfusion injury. We tested the hypothesis that goal-directed colloid - compared to crystalloid - therapy improves small intestinal, renal, and hepatic microcirculatory blood flow in pigs with ischemia/reperfusion injury. METHODS: This was a randomized trial in 32 pigs. We induced ischemia/reperfusion by supra-celiac aortic-cross-clamping. Pigs were randomized to receive either goal-directed isooncotic hydroxyethyl-starch colloid or balanced isotonic crystalloid therapy. Microcirculatory blood flow was measured using Laser-Speckle-Contrast-Imaging. The primary outcome was small intestinal, renal, and hepatic microcirculatory blood flow 4.5 h after ischemia/reperfusion. Secondary outcomes included small intestinal, renal, and hepatic histopathological damage, macrohemodynamic and metabolic variables, as well as specific biomarkers of tissue injury, renal, and hepatic function and injury, and endothelial barrier function. RESULTS: Small intestinal microcirculatory blood flow was higher in pigs assigned to isooncotic hydroxyethyl-starch colloid therapy than in pigs assigned to balanced isotonic crystalloid therapy (768.7 (677.2-860.1) vs. 595.6 (496.3-694.8) arbitrary units, p = .007). There were no important differences in renal (509.7 (427.2-592.1) vs. 442.1 (361.2-523.0) arbitrary units, p = .286) and hepatic (604.7 (507.7-701.8) vs. 548.7 (444.0-653.3) arbitrary units, p = .376) microcirculatory blood flow between groups. Pigs assigned to colloid - compared to crystalloid - therapy also had less small intestinal, but not renal and hepatic, histopathological damage. CONCLUSIONS: Goal-directed isooncotic hydroxyethyl-starch colloid - compared to balanced isotonic crystalloid - therapy improved small intestinal, but not renal and hepatic, microcirculatory blood flow in pigs with ischemia/reperfusion injury. Whether colloid therapy improves small intestinal microcirculatory blood flow in patients with ischemia/reperfusion needs to be investigated in clinical trials.

Cost-effectiveness analysis of intralesional and perilesional recombinant human epidermal growth factor vs hydrocolloid therapy in venous ulcer treatment in the Colombian context.

OBJECTIVE: To perform a comparative analysis of health care expenses and outcomes in response to the question: What is the cost-effectiveness of intralesional and perilesional recombinant human epidermal growth factor (rhEGF) compared with hydrocolloid therapy in patients diagnosed with chronic venous insufficiency without infection in Colombia? METHODS: A Markov model was used to determine cost effectiveness over a 5-year period, considering the perspective of the health system in Colombia. The study included patients aged >18 years diagnosed with chronic venous insufficiency and used clinical studies to calculate the probabilities of epithelialization, infection, recurrence, and mortality. RESULTS: RhEGF is more expensive per unit than hydrocolloids, but it is proven to be effective at healing ulcers in 8 to 12 weeks, even in complex cases. Hydrocolloids, in contrast, typically require 29.5 weeks on average, and ≤46 weeks for complex cases. Despite the cost, rhEGF is more cost effective because it achieves results comparable with hydrocolloid therapy at a lower cost per additional quality-adjusted life-year. CONCLUSIONS: Based on cost-effectiveness analysis, rhEGF is a superior alternative to hydrocolloids for treating venous ulcers in Colombia. Not only is it more affordable, but it also enhances patients' quality of life and streamlines the health care system's resource use.

Goal-directed fluid therapy using uncalibrated pulse contour analysis and balanced crystalloid solutions during hip revision arthroplasty: a quality implementation project.

BACKGROUND: To implement a goal-directed fluid therapy (GDFT) protocol using crystalloids in hip revision arthroplasty surgery within a quality management project at a tertiary hospital using a monocentric, prospective observational study. METHODS: Adult patients scheduled for elective hip revision arthroplasty surgery were screened for inclusion in this prospective study. Intraoperatively stroke volume (SV) was optimized within a previously published protocol using uncalibrated pulse contour analysis and balanced crystalloids. Quality of perioperative GDFT was assessed by protocol adherence, SV increase as well as the rate of perioperative complications. Findings were then compared to two different historical groups of a former trial: one receiving GDFT with colloids (prospective colloid group) and one standard fluid therapy (retrospective control group) throughout surgery. Statistical analysis constitutes exploratory data analyses and results are expressed as median with 25th and 75th percentiles, absolute and relative frequencies, and complication rates are further given with 95% confidence intervals for proportions using the normal approximation without continuity correction. RESULTS: Sixty-six patients underwent GDFT using balanced crystalloids and were compared to 130 patients with GDFT using balanced colloids and 130 controls without GDFT fluid resuscitation. There was a comparable increase in SV (crystalloids: 65 (54-74 ml; colloids: 67.5 (60-75.25 ml) and total volume infused (crystalloids: 2575 (2000-4210) ml; colloids: 2435 (1760-3480) ml; and controls: 2210 (1658-3000) ml). Overall perioperative complications rates were similar (42.4% (95%CI 30.3-55.2%) for crystalloids and 49.2% (95%CI 40.4-58.1%) for colloids and lower compared to controls: 66.9% (95%CI 58.1-74.9)). Interestingly, a reduced number of hemorrhagic complications was observed within crystalloids: 30% (95%CI 19.6-42.9); colloids: 43% (95%CI 34.4-52.0); and controls: 62% (95%CI 52.6-69.9). There were no differences in the rate of admission to the post-anesthesia care unit or intensive care unit as well as the length of stay. CONCLUSIONS: Perioperative fluid management using a GDFT protocol with crystalloids in hip revision arthroplasty surgery was successfully implemented in daily clinical routine. Perioperative complications rates were reduced compared to a previous management without GDFT and comparable when using colloids. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01753050.

Retrospective analysis of the use of canine-specific albumin in 125 critically ill dogs.

OBJECTIVE: To describe the clinical use of canine-specific albumin (CSA) in critically ill dogs, report adverse events, and evaluate measurable clinical effects of CSA administration. DESIGN: Retrospective case series from 2019 to 2020. SETTING: Large, urban, private-practice referral and emergency center. ANIMALS: Consecutive sample of 125 client-owned dogs administered CSA transfusions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The conditions most commonly associated with the use of CSA were surgical (32/125) and nonsurgical (20/125) gastrointestinal disease. Both serum albumin and total plasma protein concentrations were significantly increased posttransfusion (P < 0.001), and 16% albumin transfusions produced the greatest magnitude increase in serum albumin (P = 0.0015). Concurrent crystalloid administration did not affect change in albumin. While there was no significant improvement in blood pressure seen in those patients that received albumin, a significant improvement in shock index was identified (P = 0.02). Adverse events were uncommon; however, 8 critically ill dogs died during CSA administration. CONCLUSIONS: CSA appears to be a relatively safe alternative to synthetic colloids and complementary to crystalloids in critically ill patients. More concentrated solutions may be more effective in raising serum albumin concentration. Further investigation into the indications for and efficacy of CSA will continue to improve our knowledge of this blood product.

Fluid management in children with severe dengue: a narrative review.

Dengue is a mosquito-borne arboviral infection of increasing public health importance. Globally, children account for a significant proportion of infections. No pathogen-specific treatment currently exists, and the current approach to reducing disease burden is focused on preventative strategies such as vector control, epidemiological interventions, and vaccination in selected populations. Once infected, the mainstay of treatment is supportive, of which appropriate fluid management is a cornerstone. The timely provision of fluid boluses has historically been central to the management of septic shock. However, in patients with dengue shock, particular emphasis is placed on judicious fluid administration. Certain colloids such as hydroxyethyl starches and dextran, despite no longer being used routinely in intensive care units due to concerns of acute kidney injury and impairment of coagulation, are still commonly used in dengue shock syndrome. Current guidelines recommend initial crystalloid therapy, with consideration of colloids for severe or recalcitrant shock in patients with dengue. In this review, we discuss the pathophysiology of septic shock, and consider whether any differences in dengue exist that may warrant a separate approach to fluid therapy. We critically review the available evidence for fluid management in dengue, including the role of colloids. In dengue, there is increasing recognition of the importance of tailoring fluid therapy to phases of disease, with attention to the need for fluid "deresuscitation" once the critical phase of vascular leak passes.

Fluids in the ICU: which is the right one?

The administration of fluids is one of the most common interventions in the intensive care unit. The effects and side effects of intravenous fluids depend on the amount administered and their specific composition. Intravenous fluid solutions are either considered crystalloids (for example 0.9% saline, lactated Ringer's solution) or colloids (artificial colloids such as gelatins, and albumin). This narrative review summarizes the physiological principles of fluid therapy and reviews the most important studies on crystalloids, artificial colloids and albumin in the context of critically ill patients.

Fluid Therapy for the Emergent Small Animal Patient: Crystalloids, Colloids, and Albumin Products.

Water is essential for life. Without adequate fluid intake, normal body functioning becomes impaired and ultimately can lead to death. A fluid therapy plan should be considered for any small animal patient that has either inadequate fluid intake, excessive fluid loss, or both. A simplified approach to fluid therapy begins with an understanding of the composition of fluid and its distribution within the body. Next, consideration of electrolyte loss, acid-base disturbances, perfusion impairment, and loss of protein also becomes important when replenishing deficits by using various fluids that are commercially available to small animal practitioners.

Balanced Salt Solutions for Critically Ill Patients: Nonplused and Back to Basics.

OBJECTIVES: The purpose of this article is to summarize the results of major randomized controlled trials (RCTs) comparing clinical outcomes of critically ill patients treated with normal saline (NS) or balanced salt solutions (BSSs), address discordant results of these studies, and provide direction for future investigations. DATA SOURCES: PubMed (2011 to January 2022) with bibliographies of retrieved articles searched for additional articles. STUDY SELECTION AND DATA EXTRACTION: RCTs comparing NS and BSSs in critically ill adult patients. DATA SYNTHESIS: Recently published large RCTs comparing NS with BSSs in heterogeneous populations of intensive care unit patients did not find significant differences in mortality, despite positive findings in some end points in prior RCTs. However, there were a number of methodologic issues common to the RCTs including: varying study designs and end points, clinician discretion for the majority or all treatments other than the primary intervention fluid, heterogeneous patients with varying levels of acuity, and lack of power to investigate potential subgroup differences. In addition, there were problematic issues related to blinding and use of nonstudy fluids. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Intravenous fluids are a mainstay of supportive care for critically ill patients. Similar to the so-called crystalloid-colloid debate, there has been a long-standing debate among critical care clinicians and researchers concerning the preferred crystalloid solution, NS versus one of the available BSSs. CONCLUSIONS: Despite the recent publication of large multicenter RCTs, the preferred resuscitation fluid, NS or a BSS, for critically ill patients is still open for debate, although the available investigations do provide some direction for clinicians and for future investigations.

The Evolution of Colloid Administration in Burn Resuscitation.

ABSTRACT: Colloid administration in acute resuscitation of burn injuries is being increasingly recognized as an important part of fluid management for these injuries. Such clinical experience, along with possibilities of endothelial preservation by colloid solutions, could lead to a major reconsideration of early colloid administration in burn resuscitation.

Colloid coload versus crystalloid coload to prevent maternal hypotension in women receiving prophylactic phenylephrine infusion during caesarean delivery: a randomised controlled trial.

BACKGROUND: The optimal fluid strategy to prevent maternal hypotension during caesarean delivery remains unclear. This study aim was to compare the incidence of post-spinal anaesthesia hypotension in women receiving either colloid or crystalloid coload in the setting of prophylactic phenylephrine infusion during caesarean delivery. METHODS: Healthy mothers undergoing elective caesarean delivery under spinal anaesthesia were randomised to receive a rapid intravenous coload with 6% hydroxyethyl starch 130/0.4 10 mL/kg (colloid group) or balanced crystalloid solution (Plasma Solution A) 10 mL/kg (crystalloid group) during spinal anaesthesia. All women had a prophylactic phenylephrine infusion initiated at 25 µg/min immediately after the subarachnoid block and titrated to systolic blood pressure using a standardised protocol. The primary outcome was the incidence of hypotension (systolic blood pressure <80% of baseline) until delivery. RESULTS: The incidence of hypotension was 50% in the colloid group and 62% in the crystalloid group (absolute difference, -12% [95% CI -33% to 9%]; relative risk, 0.8 [95% CI 0.56 to 1.14]; P=0.314). No significant difference between groups was found in the number of hypotensive episodes (median 0.5 [IQR 0 to 1] vs 1 [0 to 2], P=0.132) or phenylephrine dose (675 [IQR 425 to 975] µg vs 750 [625 to 950] µg, P=0.109). The incidence of severe hypotension, symptomatic hypotension, bradycardia, nausea, and the neonatal outcomes were not significantly different. CONCLUSIONS: This study found no benefit of colloid coload compared with crystalloid coload for preventing maternal hypotension in the presence of prophylactic phenylephrine infusion during caesarean delivery.

A review of adult resuscitative fluid purchasing and usage trends at an academic tertiary hospital in Johannesburg.

BACKGROUND: Intravenous fluid administration is a vital component in the resuscitation of critically ill patients. In recent years, there have been many studies to help guide which fluids should be used for resuscitation. Currently, it appears that the international trend is away from the use of colloids and unbalanced crystalloids and towards the use of balanced crystalloids. The aim of our study was to determine whether evolving international evidence has impacted resuscitative fluid practices in the Emergency Department (ED) and the Intensive Care Unit (ICU) in a tertiary hospital in South Africa. METHODS: The study design was two-fold: a cross-sectional physician survey and a retrospective longitudinal observational study of the pharmacy fluid purchase records from the combined ED and ICU. RESULTS: Cross-sectional survey: in 2020 a doctor was 8.3 times more likely to choose a balanced crystalloid for resuscitation regardless of the clinical scenario over any other fluid (CI: 5.0-13.8). 55% of doctors surveyed agreed that their resuscitation fluid of choice had changed for a variety of reasons with the most popular reason cited as post-graduate education. Retrospective longitudinal observational study: throughout the study period, balanced crystalloids were the majority fluid purchased, although in ED lactated Ringers was the preferred balanced crystalloid and in ICU PlasmaLyte was preferred. Minimal colloids were purchased over the study period in declining amounts. CONCLUSIONS: Doctors working in a tertiary hospital in South Africa are following the trend of current evidence by using a balanced crystalloid as their resuscitation fluid of choice.

Trends in Prehospital Blood, Crystalloid, and Colloid Administration in Accordance With Changes in Tactical Combat Casualty Care Guidelines.

INTRODUCTION: Hemorrhage is the leading threat to the survival of battlefield casualties. This study aims to investigate the types of fluids and blood products administered in prehospital trauma encounters to discover the effectiveness of Tactical Combat Casualty Care (TCCC) recommendations. MATERIALS AND METHODS: This is a secondary analysis of a previously described dataset from the Department of Defense Trauma Registry with a focus on prehospital fluid and blood administration in conjunction with changes in the TCCC guidelines. We collected demographic information on each patient. We categorized receipt of each fluid type and blood product as a binary variable for each casualty and evaluated trends over 2007-2020 both unadjusted and controlling for injury severity and mechanism of injury. RESULTS: Our original dataset comprised 25,897 adult casualties from January 1, 2007 through March 17, 2020. Most (97.3%) of the casualties were male with a median age of 25. Most (95.5%) survived to hospital discharge, and 12.2% of the dataset received fluids of any kind. Medical personnel used crystalloids in 7.4% of encounters, packed red blood cells in 2.0%, and whole blood in 0.5% with very few receiving platelets or freeze-dried plasma. In the adjusted model, we noted significant year-to-year increases in intravenous fluid administration from 2014 to 2015 and 2018 to 2019, with significant decreases noted in 2008-2009, 2010-2012, and 2015-2016. We noted no significant increases in Hextend used, but we did note significant decreases in 2010-2012. For any blood product, we noted significant increases from 2016 to 2017, with decreases noted in 2009-2013, 2015-2016, and 2017-2018. Overall, we noted a general spike in all uses in 2011-2012 that rapidly dropped off 2012-2013. Crystalloids consistently outpaced the use of blood products. We noted a small upward trend in all blood products from 2017 to 2019. CONCLUSIONS: Changes in TCCC guidelines did not immediately translate into changes in prehospital fluid administration practices. Crystalloid fluids continue to dominate as the most commonly administered fluid even after the 2014 TCCC guidelines changed to use of blood products over crystalloids. There should be future studies to investigate the reasons for delay in guideline implementation and efforts to improve adherence.

[Volume management: peri-operatively and peri-interventionally]. / Perioperatives und periinterventionelles Volumenmanagement.

Fluid therapy is one of the basic and most frequently performed medical therapies in everyday clinical practice. However, optimal volume management is a challenge: the application is simple, but the whole volume management is a complex process and physicians have to pay attention on underlying pathophysiology. Intravenous fluids should be prescribed like medications, i. e. the type of fluid and the amount must be adapted to each individual patient with his needs. Intravascular volume therapy is often used peri-operatively and peri-interventionally.Nowadays, crystalloid solutions are widely used and the standard is a balanced electrolyte solution. Only in selected situations 0,9 % sodium chloride solutions should be used, because they contain a high chloride concentration (154 mmol/l) and lead to increased risk of hyperchloremic metabolic acidosis.

Adoption of rescue colloid during burn resuscitation decreases fluid administered and restores end-organ perfusion.

INTRODUCTION: Traditionally, lactated Ringer's solution (LR) has been utilized for the resuscitation of thermally injured patients via the Parkland or Brooke formulas. Both of these formulas include colloid supplementation after 24 h of resuscitation. Recently, the addition of albumin within the initial resuscitation has been reported to decrease fluid creep and hourly fluids given. Our institution has previously advocated for a crystalloid-driven resuscitation. Given reports of improved outcomes with albumin, we pragmatically adjusted these practices and present our findings for doing so. METHODS: Our burn registry, consisting of prospectively collected patient data, was queried for those at least 18 years of age who, between July 2017 and December 2018, sustained a thermal injury and completed a formal resuscitation (24 h). At the attending physician's discretion, rescue colloid was administered using 25% albumin for those failing to respond to traditional resuscitation (patients with sustained urine output of <0.5 mL/kg over 2-3 h, or unstable vital signs and ongoing fluid administration). We compared the total volume of the crystalloid-only and rescue colloid resuscitation fluids given to patients. We also examined the in/out fluid balances during resuscitation. Statistical analysis was performed using Stata software. RESULTS: A total of 91 patients with thermal injuries were included: the median age was 40 (IQR 31-57), 73% were male, and 30 patients received rescue albumin. The percentage of total body surface area burned (%TBSA) was greater in those who received rescue albumin (40.3% vs. 34%; p = 0.047). Despite a higher %TBSA in the albumin group, the total LR given during resuscitation was not significantly different between groups (15,914.43 mL vs. 11,828.71 mL; p = 0.129) even when normalized for TBSA and weight (ml LR/kg/%TBSA: 4.31 vs. 3.66; p = 0.129. The average in/out fluid ratio for the rescue group was higher than for the crystalloid group (0.83 ± 0.05 vs. 0.59 ± 0.11; p = 0.06) and returned to normal after colloid administration. CONCLUSION: Rescue albumin administration decreases the amount of fluid administered per %TBSA during resuscitation, and also increases end organ function as evidenced by increased urinary output. These effects occurred in patients who sustained larger burns and failed to respond to traditional crystalloid resuscitation. Our findings led us to modify our current protocol and a related prospective study of clinical outcomes.

High-Throughput Screening for Colloidal Stability of Peptide Formulations Using Dynamic and Static Light Scattering.

Selection of an appropriate formulation to stabilize therapeutic proteins against aggregation is one of the most challenging tasks in early-stage drug product development. The amount of aggregates is more difficult to quantify in the case of peptides due to their small molecular size. Here, we investigated the suitability of diffusion self-interaction parameters (kD) and osmotic second virial coefficients (B22) for high-throughput (HT) screening of peptide formulations regarding their aggregation risk. These parameters were compared to the effect of thermal stress on colloidal stability. The formulation matrix comprised six buffering systems at two selected pH values, four tonicity agents, and a common preservative. The results revealed that electrostatic interactions are the main driver to control colloidal stability. Preferred formulations consisted of acetate and succinate buffer at pH 4.5 combined with glycerol or mannitol and optional m-cresol. kD proved to be a suitable surrogate for B22 as an indicator of high colloidal stability in the case of peptides as was previously described for globular proteins and antibodies. Formulation assessment solely based on kD obtained by HT methods offers important insights into the optimization of colloidal stability during the early development of peptide-based liquid formulations and can be performed with a limited amount of peptide (∼360 mg).

[Comments on the updated German S3 guidelines on intravascular volume therapy in adults]. / Kommentar zur aktualisierten S3-Leitlinie zur intravasalen Volumentherapie beim Erwachsenen.

The German S3 guidelines on intravascular volume therapy in adults were updated in September 2020. Based on updated evidence recommendations for the diagnosis of isotonic dehydration and for fluid therapy with crystalloids and colloids in peri-interventional and intensive care medicine were proposed.