Anesthesia-Associated Relative Hypovolemia: Mechanisms, Monitoring, and Treatment Considerations.

Although the utility and benefits of anesthesia and analgesia are irrefutable, their practice is not void of risks. Almost all drugs that produce anesthesia endanger cardiovascular stability by producing dose-dependent impairment of cardiac function, vascular reactivity, and compensatory autoregulatory responses. Whereas anesthesia-related depression of cardiac performance and arterial vasodilation are well recognized adverse effects contributing to anesthetic risk, far less emphasis has been placed on effects impacting venous physiology and venous return. The venous circulation, containing about 65-70% of the total blood volume, is a pivotal contributor to stroke volume and cardiac output. Vasodilation, particularly venodilation, is the primary cause of relative hypovolemia produced by anesthetic drugs and is often associated with increased venous compliance, decreased venous return, and reduced response to vasoactive substances. Depending on factors such as patient status and monitoring, a state of relative hypovolemia may remain clinically undetected, with impending consequences owing to impaired oxygen delivery and tissue perfusion. Concurrent processes related to comorbidities, hypothermia, inflammation, trauma, sepsis, or other causes of hemodynamic or metabolic compromise, may further exacerbate the condition. Despite scientific and technological advances, clinical monitoring and treatment of relative hypovolemia still pose relevant challenges to the anesthesiologist. This short perspective seeks to define relative hypovolemia, describe the venous system's role in supporting normal cardiovascular function, characterize effects of anesthetic drugs on venous physiology, and address current considerations and challenges for monitoring and treatment of relative hypovolemia, with focus on insights for future therapies.

A Systematic Review of the Quality of IV Fluid Therapy in Veterinary Medicine.

OBJECTIVE: To evaluate the quality of the veterinary literature investigating IV fluid therapy in dogs, cats, horses, and cattle. DESIGN: Systematic review. PROCEDURES: The preferred reporting of items for systematic review and meta-analysis protocols (PRISMA-P) was employed for systematic review of all relevant IV fluid therapy manuscripts published from January 1969 through December 2016 in the Commonwealth Agricultural Bureaux International (CABI) database. Independent grading systems used to evaluate manuscripts included the updated CONsolidated Standards of Reporting Trials 2012 checklist, risk of bias for animal intervention studies, criteria for levels of evidence, and methodological quality (Jadad scale). The quality of articles published before and after 2010 was compared. RESULTS: One hundred and thirty-nine articles (63 dogs, 7 cats, 39 horses, 30 cattle) from 7,258 met the inclusion criteria. More than 50% of the manuscripts did not comply with minimal requirements for reporting randomized controlled trials. The most non-compliant items included identification of specific predefined objectives or a hypothesis, identification of trial design, how sample size was determined, randomization, and blinding procedures. Most studies were underpowered and at risk for selection, performance, and detection bias. The overall quality of the articles improved for articles published after 2010. CONCLUSION AND CLINICAL RELEVANCE: Most of the veterinary literature investigating the administration of IV fluid therapy in dogs, cats, horses, and cattle is descriptive, does not comply with standards for evidence, or provide adequate translation to clinical practice. Authors should employ and journal editors should enforce international consensus recommendations and guidelines for publication of data from animal experiments investigating IV fluid therapy.

Evaluation of neuronal apoptosis precursors in an experimental model of acute normovolemic hemodilution.

BACKGROUND: The effects of acute anemia on neuronal cells and the safe limits of hematocrit are not well established. The objective of this study was to evaluate neuronal pro- and anti-apoptotic Bax and Bcl-x proteins, caspase-3 and -9 activity, and DNA fragmentation after acute normovolemic hemodilution (ANH). METHODS: Twenty-four pigs were anesthetized and randomized into 4 groups: Sham, ANH to 15% hematocrit (ANH15%), ANH to 10% hematocrit (ANH10%) and hypoxia (Hx). ANH was achieved by simultaneous blood withdrawal and hydroxyethyl starch infusion. Hx consisted of ventilation with a 6% inspired oxygen fraction for 60 minutes. Bax and Bcl-x proteins as well as DNA fragmentation were evaluated in cortical nuclear and mitochondrial fractions. Caspase-3 and -9 activity was evaluated in the cortical mitochondrial and hippocampal cytosolic fractions. The data were compared using analysis of variance followed by Tukey's test (P<0.05). RESULTS: No changes were observed in Bax protein expression after hemodilution in the ANH15% and ANH10% groups compared to the Sham group. Bax expression in the Hx group was increased in the nuclear and mitochondrial fractions compared to all other groups. No significant difference was observed in Bcl-x expression. Caspase-3 and -9 activity in the cytosolic and mitochondrial fractions was different in the Hx group compared to all other groups. No statistical significance in DNA fragmentation was found among the Sham, ANH15% or ANH10% groups. CONCLUSION: ANH to 10 and 15% hematocrit did not induce alterations in apoptosis precursors, suggesting that cerebral oxygenation was preserved during these anemic states.

Pulse pressure variation is comparable with central venous pressure to guide fluid resuscitation in experimental hemorrhagic shock with endotoxemia.

INTRODUCTION: Pulse pressure variation (PPV) has been proposed as a promising resuscitation goal, but its ability to predict fluid responsiveness has been questioned in various conditions. The purpose of this study was to assess the performance of PPV in predicting fluid responsiveness in experimental hemorrhagic shock with endotoxemia, while comparing it with goals determined by a conventional set of guidelines. METHODS: Twenty-seven pigs were submitted to acute hemorrhagic shock with intravenous infusion of endotoxin and randomized to three groups: (i) control; (ii) conventional treatment with crystalloids to achieve and maintain central venous pressure (CVP) 12 to 15 mmHg, mean arterial pressure of 65 mmHg or greater, and SvO2 (mixed venous oxygen saturation) of 65% or greater; (iii) treatment to achieve and maintain PPV of 13% or less. Parametric data were analyzed by two-way analysis of variance and Tukey test and differences in crystalloid volumes by t test. Predictive values of variables regarding fluid responsiveness were evaluated by receiver operating characteristic curves and multiple logistic regression. RESULTS: Both treatments produced satisfactory hemodynamic recovery, without statistical differences in fluid administration (P = 0.066), but conventional treatment induced higher CVP (P = 0.001). Areas under receiver operating characteristic curves were larger for CVP (0.77; 95% confidence interval, 0.68-0.86) and PPV (0.74; 95% confidence interval, 0.65-0.83), and these variables were further selected by multiple logistic regression as independent predictors of responsiveness. Optimal PPV cutoff was 15%, with false-positive results involving mean pulmonary arterial pressure of 27 mmHg or greater. CONCLUSIONS: Acute resuscitation guided by PPV was comparable with the strategy guided by CVP, mean arterial pressure, and SvO2. Central venous pressure and PPV were individually limited but independently predictive of fluid responsiveness.

Comparison of the effects of tramadol, codeine, and ketoprofen alone or in combination on postoperative pain and on concentrations of blood glucose, serum cortisol, and serum interleukin-6 in dogs undergoing maxillectomy or mandibulectomy.

OBJECTIVE: To compare analgesic effects of tramadol, codeine, and ketoprofen administered alone and in combination and their effects on concentrations of blood glucose, serum cortisol, and serum interleukin (IL)-6 in dogs undergoing maxillectomy or mandibulectomy. ANIMALS: 42 dogs with oral neoplasms. PROCEDURES: 30 minutes before the end of surgery, dogs received SC injections of tramadol (2 mg/kg), codeine (2 mg/kg), ketoprofen (2 mg/kg), tramadol+ketoprofen, or codeine+ketoprofen (at the aforementioned dosages). Physiologic variables, analgesia, and sedation were measured before (baseline) and 1, 2, 3, 4, 5, and 24 hours after surgery. Blood glucose, serum cortisol, and serum IL-6 concentrations were measured 1, 3, 5, and 24 hours after administration of analgesics. RESULTS: All treatments provided adequate postoperative analgesia. Significant increases in mean+/-SD blood glucose concentrations were detected in dogs receiving tramadol (96+/-14 mg/dL), codeine (120+/-66 mg/dL and 96+/-21 mg/dL), ketoprofen (105+/-22 mg/dL), and codeine+ketoprofen (104+/-16 mg/dL) at 5, 1 and 3, 5, and 3 hours after analgesic administration, respectively, compared with preoperative (baseline) values. There were no significant changes in physiologic variables, serum IL-6 concentrations, or serum cortisol concentrations. Dogs administered codeine+ketoprofen had light but significant sedation at 4, 5, and 24 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Opioids alone or in combination with an NSAID promoted analgesia without adverse effects during the 24-hour postoperative period in dogs undergoing maxillectomy or mandibulectomy for removal of oral neoplasms.

Bupivacaine 0.25% and methylene blue spread with epidural anesthesia in dog.

OBJECTIVE: To evaluate the extent sensory and motor blocks produced by the epidural injection of different volumes of 0.25% bupivacaine (Bu) with methylene blue (MB), in dogs. STUDY DESIGN: Prospective experimental trial. ANIMALS: Twenty healthy adult mongrel dogs, weighing 9.9 +/- 1.9 kg. METHODS: Dogs were randomly allocated into one of four groups that received 0.2, 0.4, 0.6 or 0.8 mL kg(-1) of an epidural solution containing 0.25% Bu and MB. Sensory block was evaluated against time by pinching the tail, hind limb interdigital web, toenail bases and the skin over the vertebral dermatomes. Motor block was assessed by ataxia, hind limb weight-bearing ability and by loss of muscle tone of the tail and pelvic limbs. Data were collected at 2, 5, 10, 15 and 30 minutes after the end of epidural injection. After the final time point, dogs were euthanatized and laminectomies were conducted to expose the extent of the dural dye staining. RESULTS: The volumes 0.2, 0.4, 0.6 and 0.8 mL kg(-1) of 0.25% Bu and MB blocked a mean of 5, 14.2, 20.2 and 21 dermatomes, respectively. The extent of the sensory block increased up to a volume of 0.6 mL kg(-1). Motor block was longer-lasting and more intense than sensory block. Complete dyeing of the spinal cord with MB was achieved in some dogs at 0.4 mL kg(-1) and all dogs at 0.6 mL kg(-1). CONCLUSIONS: The volume of anesthetic injected into the epidural space plays an important role in the quality of the epidural anesthesia. At 0.25%, bupivacaine provided an efficient sensory block at 0.6 mL kg(-1). CLINICAL RELEVANCE: Relatively high volumes (0.6 mL kg(-1)) of 0.25%, BU and MB were needed to produce an effective sensory and motor block caudal to the umbilicus, but all spinal cord segments were reached by MB at this dose.

A comparison between pulse pressure variation and right end diastolic volume index as guides to resuscitation in a model of hemorrhagic shock in pigs.

BACKGROUND: Different hemodynamic parameters including static indicators of cardiac preload as right ventricular end-diastolic volume index (RVEDVI) and dynamic parameters as pulse pressure variation (PPV) have been used in the decision-making process regarding volume expansion in critically ill patients. The objective of this study was to compare fluid resuscitation guided by either PPV or RVEDVI after experimentally induced hemorrhagic shock. METHODS: Twenty-six anesthetized and mechanically ventilated pigs were allocated into control (group I), PPV (group II), or RVEDVI (group III) group. Hemorrhagic shock was induced by blood withdrawal to target mean arterial pressure of 40 mm Hg, maintained for 60 minutes. Parameters were measured at baseline, time of shock, 60 minutes after shock, immediately after resuscitation with hydroxyethyl starch 6% (130/0.4), 1 hour and 2 hours thereafter. The endpoint of fluid resuscitation was determined as the baseline values of PPV and RVEDVI. Statistical analysis of data was based on analysis of variance for repeated measures followed by the Bonferroni test (p < 0.05). RESULTS: Volume and time to resuscitation were higher in group III than in group II (group III = 1,305 +/- 331 mL and group II = 965 +/- 245 mL, p < 0.05; and group III = 24.8 +/- 4.7 minutes and group II = 8.8 +/- 1.3 minutes, p < 0.05, respectively). All static and dynamic parameters and biomarkers of tissue oxygenation were affected by hemorrhagic shock and nearly all parameters were restored after resuscitation in both groups. CONCLUSION: In the proposed model of hemorrhagic shock, resuscitation to the established endpoints was achieved within a smaller amount of time and with less volume when guided by PPV than when guided by pulmonary artery catheter-derived RVEDVI.