Restoring microcirculatory perfusion in a preclinical model of severe hemorrhagic shock: The role of microcirculatory function.

BACKGROUND: No reflow in capillaries (no reflow) is the lack of tissue perfusion that occurs once central hemodynamics are restored. This prevents oxygen transfer and debt repayment to vital tissues after shock resuscitation. Since metabolic swelling of cells and tissues can cause no reflow, it is a target for study in shock. We hypothesize no reflow secondary to metabolic cell swelling causes the problem not addressed by current strategies that increase central hemodynamics alone. METHODS: Anesthetized swine were bled until plasma lactate reached 7.5 mM to 9 mM. Intravenous low volume resuscitation solutions were administered (6.8 mL/kg over 5 minutes) consisting of; (1) lactated Ringer (LR), (2) autologous whole blood, (3) high-dose vitamin C (200 mg/kg), or (4) 10% PEG-20k, a polymer-based cell impermeant that corrects metabolic cell swelling. Outcomes were macrohemodynamics (MAP), plasma lactate, capillary flow in the gut and tongue mucosa using orthogonal polarization spectral imaging (OPSI), and survival to 4 hours. RESULTS: All PEG-20k resuscitated swine survived 240 minutes with MAP above 60 mm Hg compared with 50% and 0% of the whole blood and LR groups, respectively. The vitamin C group died at just over 2 hours with MAPs below 40 and high lactate. The LR swine only survived 30 minutes and died with low MAP and high lactate. Capillary flow positively correlated ( p < 0.05) with survival and MAP. Sublingual OPSI correlated with intestinal OPSI and OPSI was validated with a histological technique. DISCUSSION: Targeting micro-hemodynamics in resuscitation may be more important than macrohemodynamics. Fixing both is optimal. Sublingual OPSI is clinically achievable to assess micro-hemodynamic status. Targeting tissue cell swelling that occurs during ATP depletion in shock using optimized osmotically active cell impermeants in crystalloid low volume resuscitation solutions improves perfusion in shocked tissues, which leverages a primary mechanism of injury.

Utilizing retrograde autologous priming for blood conservation in cardiac surgery.

BACKGROUND: The use of crystalloid priming for extracorporeal circuit in adult cardiac surgery causes inevitable haemodilution. The haemodilution can be reduced by using methods such as retrograde autologous priming (RAP) with the patient's blood. This study compares the RAP technique with standard priming with regards to safety and the impact on haemodilution. METHODS: This was a retrospective cohort study between a control group (n = 100) consisting of consecutive patients undergoing first time isolated coronary artery bypass surgery (CABG) with crystalloid priming solution in the circuit, and the RAP group (n = 100) consisting of patients undergoing isolated first time CABG with the RAP method. All demographics, procedure and perfusion data were gathered from the local surgical and perfusion database. RESULTS: Despite starting with comparable mean pre-operative haemoglobin (Hb) levels (control 127 mg/dL versus RAP 129 mg/dL), the RAP group had significantly higher mean post-op Hb level (109 mg/dL versus 92 mg/dL, P < 0.01). Crystalloid use was also significantly lower in RAP group (3.15 L versus 4.17 L P < 0.02). Freedom from red blood cell transfusion (86% versus 76% P = 0.038) and freedom from blood products (78% versus 66%, P = 0.032) was also significantly better in the RAP group. CONCLUSIONS: This study demonstrates that retrograde autologous priming is a safe and effective method for priming the cardiopulmonary bypass circuit in adult cardiac surgery, with significantly beneficial effects on transfusion rates and intra operative fluid requirements. Given these results the RAP method should be considered as a routine step in priming an extracorporeal circuit for adult cardiac operations.

Effects of calcium supplementation to resuscitation fluids in endurance horses: A randomized, blinded, clinical trial.

BACKGROUND: The addition of calcium to resuscitation fluids is a common practice in horses, but studies evaluating the effects of calcium supplementation are limited. In healthy horses, decreases in heart rate and changes in serum electrolyte concentrations have been reported. HYPOTHESIS: Calcium gluconate administration at a rate of 0.4 mg/kg/min to eliminated endurance horses with metabolic problems will affect heart rate, gastrointestinal sounds, and serum electrolyte concentrations. ANIMALS: Endurance horses eliminated from the Tevis Cup 100-mile (160 km) endurance ride for metabolic problems and requiring IV fluid therapy were eligible. METHODS: Sixteen horses were randomly assigned to receive 0.4 mg/kg/min of calcium (23% calcium gluconate solution) over 1 hour diluted in 10 L of a non-calcium containing isotonic crystalloid (CAL group) or 10 L of a non-calcium containing isotonic crystalloid (CON group). Staff members administering the fluids were blinded to treatment group. Blood samples were collected and physical examinations performed before and after treatment. Heart rates were recorded every 15 min during fluid administration. Data were compared using 2-way analysis of variance (ANOVA) with repeated measures for continuous variables and Fisher's exact test for categorical variables. RESULTS: Calcium was associated with lower heart rates 45 min after starting the infusion (P = .002). Gastrointestinal sounds were less likely to improve in the calcium group compared with the control group (P = .005). An increase in plasma phosphorus concentration (P = .03) was associated with calcium administration. CONCLUSIONS: Intravenous calcium supplementation to endurance horses eliminated from competition after development of metabolic problems may decrease heart rate but impairs improvement in gastrointestinal sounds.

Effects of polyethylene glycol-20k IV solution on donor management in a canine model of donor brain death.

BACKGROUND: Traditionally, vasopressors and crystalloids have been used to stabilize brain dead donors; however, the use of crystalloid is fraught with complications. This study aimed to investigate the effectiveness of a newly developed impermeant solution, polyethylene glycol-20k IV solution (PEG-20k) for resuscitation and support of brain dead organ donors. METHODS: Brain death was induced in adult beagle dogs and a set volume of PEG-20k or crystalloid solution was given thereafter. The animals were then resuscitated over 16 h with vasopressors and crystalloid as necessary to maintain mean arterial pressure of 80-100 mmHg. The kidneys were procured and cold-stored for 24 h, after which they were analyzed using the isolated perfused kidney model. RESULTS: The study group required significantly less crystalloid volume and vasopressors while having less urine output and requiring less potassium supplementation than the control group. Though the two groups' mean arterial pressure and lactate levels were comparable, the study group's kidneys showed less preservation injury after short-term reperfusion indexed by decreased lactate dehydrogenase release and higher creatinine clearance than the control group. CONCLUSIONS: The use of polyethylene glycol-20k IV solution for resuscitating brain dead donors decreases cell swelling and improves intravascular volume, thereby improving end organ oxygen delivery before procurement and so preventing ischemia-reperfusion injury after transplantation.

Order Substitutions and Education for Balanced Crystalloid Solution Use in an Integrated Health Care System and Association With Major Adverse Kidney Events.

Importance: Trials comparing balanced crystalloids with normal saline have yielded mixed results regarding reductions in kidney complications and mortality for hospitalized patients receiving intravenous fluids. Objective: To evaluate the association of a multifaceted implementation program encouraging the preferential use of lactated Ringer solution with patient outcomes and intravenous fluid-prescribing practices in a large, multilevel health care system. Design, Setting, and Participants: This type 2 hybrid implementation and comparative effectiveness study enrolled all patients 18 years or older who received 1 L or more of intravenous fluids while admitted to an emergency department and/or inpatient unit at 1 of 22 hospitals in Idaho and Utah between November 1, 2018, and February 29, 2020. An interrupted time series analysis was used to assess study outcomes before and after interventions to encourage use of lactated Ringer solution. Exposures: Implementation program combining order set modification, electronic order entry alerts, and sequential clinician-targeted education to encourage prescribing of lactated Ringer solution instead of normal saline. Main Outcomes and Measures: The primary implementation outcome was the patient-level proportion of intravenous fluids that was balanced crystalloids. The primary effectiveness outcome was the incidence of major adverse kidney events (MAKE30)-a composite of new persistent kidney dysfunction, new initiation of dialysis, and death-at 30 days. Results: Among 148 423 patients (median [IQR] age, 47 [30-67] years; 91 302 women [61%]), the proportion of total fluids received that was lactated Ringer solution increased from 28% to 75% in the first week vs the last week of the study (immediate implementation effect odds ratio [OR], 3.44; 95% CI, 2.79-4.24). The estimated MAKE30 absolute risk reduction was 2.2% (95% CI, 1.3%-3.3%) based on interrupted time series analysis showing a decrease in the week-on-week trend for MAKE30 (OR difference, 0.03; 95% CI, 0.03-0.03, P < .001). The immediate postimplementation OR for MAKE30 was 0.88 (95% CI, 0.76-1.01), with a decrease in persistent kidney dysfunction (OR, 0.80; 95% CI, 0.69-0.93) and mortality (OR, 0.78; 95% CI, 0.65-0.93) but not dialysis (OR, 1.00; 95% CI, 0.76-1.32). Conclusions and Relevance: In this comparative effectiveness study, an implementation program was associated with an increase in the proportion of fluids administered as lactated Ringer solution compared with normal saline and was associated with a reduction in MAKE30 events among patients treated in a large integrated health care system.

Hematic Antegrade Repriming: A Reproducible Method to Decrease the Cardiopulmonary Bypass Insult.

The current practice of cardiopulmonary bypass (CPB) requires a preoperative priming of the circuit that is frequently performed with crystalloid solutions. Crystalloid priming avoids massive embolism but is unable to eliminate all microbubbles contained in the circuit. In addition, it causes a sudden hemodilution which is correlated with transfusion requirements and an increased risk of cognitive impairment. Several repriming techniques using autologous blood, collectively termed retrograde autologous priming (RAP), have been demonstrated to reduce the hemodilutional impact of CPB. However, the current heterogeneity in the practice of RAP limits its evidence and benefits. Here, we describe hematic antegrade repriming as an easy and reliable method that could be applied with any circuit in the market to decrease transfusion requirements, emboli, and inflammatory responses, reducing costs and the impact of CPB on postoperative recovery.

Forgot calcium? Admission ionized-calcium in two civilian randomized controlled trials of prehospital plasma for traumatic hemorrhagic shock.

BACKGROUND: Randomized clinical trials (RCTs) support the use of prehospital plasma in traumatic hemorrhagic shock, especially in long transports. The citrate added to plasma binds with calcium, yet most prehospital trauma protocols have no guidelines for calcium replacement. We reviewed the experience of two recent prehospital plasma RCTs regarding admission ionized-calcium (i-Ca) blood levels and its impact on survival. We hypothesized that prehospital plasma is associated with hypocalcemia, which in turn is associated with lower survival. METHODS: We studied patients enrolled in two institutions participating in prehospital plasma RCTs (control, standard of care; experimental, plasma), with i-Ca collected before calcium supplementation. Adults with traumatic hemorrhagic shock (systolic blood pressure ≤70 mm Hg or 71-90 mm Hg + heart rate ≥108 bpm) were eligible. We use generalized linear mixed models with random intercepts and Cox proportional hazards models with robust standard errors to account for clustered data by institution. Hypocalcemia was defined as i-Ca of 1.0 mmol/L or less. RESULTS: Of 160 subjects (76% men), 48% received prehospital plasma (median age, 40 years [interquartile range, 28-53 years]) and 71% suffered blunt trauma (median Injury Severity Score [ISS], 22 [interquartile range, 17-34]). Prehospital plasma and control patients were similar regarding age, sex, ISS, blunt mechanism, and brain injury. Prehospital plasma recipients had significantly higher rates of hypocalcemia compared with controls (53% vs. 36%; adjusted relative risk, 1.48; 95% confidence interval [CI], 1.03-2.12; p = 0.03). Severe hypocalcemia was significantly associated with decreased survival (adjusted hazard ratio, 1.07; 95% CI, 1.02-1.13; p = 0.01) and massive transfusion (adjusted relative risk, 2.70; 95% CI, 1.13-6.46; p = 0.03), after adjustment for confounders (randomization group, age, ISS, and shock index). CONCLUSION: Prehospital plasma in civilian trauma is associated with hypocalcemia, which in turn predicts lower survival and massive transfusion. These data underscore the need for explicit calcium supplementation guidelines in prehospital hemotherapy. LEVEL OF EVIDENCE: Therapeutic, level II.

Blood and fluid management during scoliosis surgery: a single-center retrospective analysis.

AIM: In the present retrospective study in scoliosis surgery, we hypothesized that application of a protocol for blood and fluid management, based on goal-directed fluid therapy, cell salvage and tranexamic acid, could lead to reduced allogeneic red blood cells transfusion. METHODS AND MATERIAL: Thirty-five patients, with American Society of Anesthesiologists physical status I/III, between 14 and 18 years scheduled for elective orthopedic surgery of scoliosis, with a planned intensive care unit admission, were enrolled in a retrospective observational study. Patients were divided in two groups. Patients in no-protocol group (Group noPro, n = 18) received a liberal intraoperative fluid therapy and patients in protocol group (Group Pro, n = 17) received fluid therapy managed according to a stroke volume variation-based protocol. The protocol included fluid therapy according to SVV monitor, permissive hypotension, tranexamic acid infusion, restrictive RBC trigger and use of perioperative cell savage. STATISTICAL ANALYSIS USED: Student's t test (2-tailed), Mann-Whitney test, Chi square test were used for statistical analysis of the data. RESULTS: There were no significant differences between the two groups in demographic data and clinical characteristics. Infused crystalloids (p = .003) and transfused allogeneic red blood cells (p = .015) were lesser in Group Pro compared to Group noPro. On the other hand, diuresis (p < .001) and vasopressors administration (p = .042) were higher in Group Pro than in Group noPro. CONCLUSION: The application of a protocol for blood and fluid management, based on goal-directed fluid therapy, cell salvage and tranexamic acid, was associated with less crystalloid fluid administration, less perioperative RBC transfusions and significantly better diuresis than patients in the no-protocol group in scoliosis surgery. REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03814239.

The effects of crystalloid warming on maternal body temperature and fetal outcomes: a randomized controlled trial / Os efeitos do aquecimento de cristaloides sobre a temperatura corporal materna e nas condições fetais: ensaio clínico randômico

Abstract Background and objectives: Hypothermia occurs in about 60% of patients under anesthesia and is generally not managed properly during short lasting surgical procedures. Hypothermia is associated with adverse clinical outcomes. The current study is designed to assess the effects of crystalloid warming on maternal and fetal outcomes in patients undergoing elective cesarean section with spinal anesthesia. Methods: In this prospective randomized controlled trial, sixty parturients scheduled for elective cesarean section with spinal anesthesia were randomly allocated to receive crystalloid at room temperature or warmed at 37 °C. Spinal anesthesia was performed at L3-L4 interspace with 10 mg of hyperbaric bupivacaine without adding opioids. Core temperature, shivering, and hemodynamic parameters were measured every minute until 10th minute and 5-min intervals until the end of operation. The primary outcome was maternal core temperature at the end of cesarean section. Results: There was no difference for baseline tympanic temperature measurements but the difference was significant at the end of the operation (p = 0.004). Core temperature was 36.8 ± 0.5 °C at baseline and decreased to 36.3 ± 0.5 °C for isothermic warmed crystalloid group and baseline tympanic core temperature was 36.9 ± 0.4 °C and decreased to 35.8 ± 0.7 °C for room temperature group at the end of the operation. Shivering was observed in 43.3% in the control group. Hemodynamic parameter changes and demographic data were not significant between groups. Conclusions: Isothermic warming crystalloid prevents the decrease in core temperature during cesarean section with spinal anesthesia in full-term parturients. Fetal Apgar scores at first and fifth minute are higher with isothermic warming.

Resumo Justificativa e objetivos: A hipotermia ocorre em cerca de 60% dos pacientes sob anestesia e geralmente não é tratada adequadamente durante procedimentos cirúrgicos de curta duração. A hipotermia está associada a desfechos clínicos adversos. O presente estudo teve como objetivo avaliar os efeitos do aquecimento de cristaloides nas condições maternas e fetais em pacientes submetidas à cesariana eletiva com raquianestesia. Métodos: Neste estudo prospectivo, randômico e controlado, 60 parturientes agendadas para cesárea eletiva com raquianestesia foram distribuídas aleatoriamente para receber cristaloides à temperatura ambiente ou aquecidos a 37 °C. A raquianestesia foi realizada no interespaço L3-L4 com 10 mg de bupivacaína hiperbárica sem adição de opioides. Temperatura central, tremores e parâmetros hemodinâmicos foram medidos a cada minuto até o décimo minuto e em intervalos de 5 min até o fim da operação. O desfecho primário foi a temperatura central materna ao final da cesárea. Resultados: Não houve diferença nas mensurações basais da temperatura timpânica, mas a diferença foi significativa no fim da operação (p = 0,004). A temperatura central foi de 36,8 ± 0,5 °C na fase basal e diminuiu para 36,3 ± 0,5 °C no grupo com aquecimento isotérmico de cristaloides e a temperatura basal timpânica foi de 36,9 ± 0,4 °C e diminuiu para 35,8 ± 0,7 °C no grupo sem aquecimento das soluções no fim da operação. Tremores foram observados em 43,3% no grupo controle. Alterações nos parâmetros hemodinâmicos e dados demográficos não foram significantes entre os grupos. Conclusões: O aquecimento isotérmico de cristaloides previne a redução da temperatura central durante a cesariana com raquianestesia em parturientes a termo. Os escores de Apgar para os fetos no primeiro e quinto minutos são maiores com o aquecimento isotérmico.

[The effects of crystalloid warming on maternal body temperature and fetal outcomes: a randomized controlled trial]. / Os efeitos do aquecimento de cristaloides sobre a temperatura corporal materna e nas condições fetais: ensaio clínico randômico.

BACKGROUND AND OBJECTIVES: Hypothermia occurs in about 60% of patients under anesthesia and is generally not managed properly during short lasting surgical procedures. Hypothermia is associated with adverse clinical outcomes. The current study is designed to assess the effects of crystalloid warming on maternal and fetal outcomes in patients undergoing elective cesarean section with spinal anesthesia. METHODS: In this prospective randomized controlled trial, sixty parturients scheduled for elective cesarean section with spinal anesthesia were randomly allocated to receive crystalloid at room temperature or warmed at 37°C. Spinal anesthesia was performed at L3-L4 interspace with 10mg of hyperbaric bupivacaine without adding opioids. Core temperature, shivering, and hemodynamic parameters were measured every minute until 10th minute and 5-min intervals until the end of operation. The primary outcome was maternal core temperature at the end of cesarean section. RESULTS: There was no difference for baseline tympanic temperature measurements but the difference was significant at the end of the operation (p=0.004). Core temperature was 36.8±0.5°C at baseline and decreased to 36.3±0.5°C for isothermic warmed crystalloid group and baseline tympanic core temperature was 36.9±0.4°C and decreased to 35.8±0.7°C for room temperature group at the end of the operation. Shivering was observed in 43.3% in the control group. Hemodynamic parameter changes and demographic data were not significant between groups. CONCLUSIONS: Isothermic warming crystalloid prevents the decrease in core temperature during cesarean section with spinal anesthesia in full-term parturients. Fetal Apgar scores at first and fifth minute are higher with isothermic warming.

An online survey of small animal veterinarians regarding current fluid therapy practices in dogs and cats.

OBJECTIVE To determine common fluid therapy practices of small animal practitioners and identify fluid therapy-related knowledge gaps that may benefit from improved educational efforts, targeted research, or both. DESIGN Online survey. SAMPLE 1,496 small animal veterinarians PROCEDURES An online survey was provided to members of the Veterinary Information Network between December 23, 2013, and January 30, 2014. The survey consisted of 24 questions investigating the administration of crystalloid and synthetic colloid solutions, but not blood products, and focused primarily on the choice of fluid type, frequency of administration, type of patient treated with fluids, treatment with fluids subcutaneously versus IV, and potassium supplementation of fluids. Only responses from practicing small animal veterinarians were included. Not all respondents answered every question, and some questions allowed > 1 answer. RESULTS Balanced crystalloid solutions were the most common fluid type in all clinical scenarios described. The most common maintenance IV fluid rate reported by respondents (762/1,333 [57%]) was 60 mL/kg/d (27 mL/lb/d); calculation of fluid administration rate by means of body surface area was infrequent. Challenges of fluid therapy included determining the appropriate rate (572/1,496 [38%]) and fluid type (497/1,496 [33%]) and determining the need for potassium supplementation (229/1,496 [15%]). CONCLUSIONS AND CLINICAL RELEVANCE Small animal veterinarians tended to favor isotonic balanced crystalloid solutions for IV fluid therapy, compared with other common choices such as isotonic saline (0.9% NaCl) solution. Despite its ubiquity, respondents found many aspects of fluid therapy to be challenging, suggesting the need for easy to use, evidence-based guidelines.

Cardiac performance is limited by oxygen delivery to the mitochondria in the crystalloid-perfused working heart.

The left ventricular working, crystalloid-perfused heart is used extensively to evaluate basic cardiac function, pathophysiology, and pharmacology. Crystalloid-perfused hearts may be limited by oxygen delivery, as adding oxygen carriers increases myoglobin oxygenation and improves myocardial function. However, whether decreased myoglobin oxygen saturation impacts oxidative phosphorylation (OxPhos) is unresolved, since myoglobin has a much lower affinity for oxygen than cytochrome c oxidase (COX). In the present study, a laboratory-based synthesis of an affordable perfluorocarbon (PFC) emulsion was developed to increase perfusate oxygen carrying capacity without impeding optical absorbance assessments. In left ventricular working hearts, along with conventional measurements of cardiac function and metabolic rate, myoglobin oxygenation and cytochrome redox state were monitored using a novel transmural illumination approach. Hearts were perfused with Krebs-Henseleit (KH) or KH supplemented with PFC, increasing perfusate oxygen carrying capacity by 3.6-fold. In KH-perfused hearts, myoglobin was deoxygenated, consistent with cytoplasmic hypoxia, and the mitochondrial cytochromes, including COX, exhibited a high reduction state, consistent with OxPhos hypoxia. PFC perfusate increased aortic output from 76 ± 6 to 142 ± 4 ml/min and increased oxygen consumption while also increasing myoglobin oxygenation and oxidizing the mitochondrial cytochromes. These results are consistent with limited delivery of oxygen to OxPhos resulting in an adapted lower cardiac performance with KH. Consistent with this, PFCs increased myocardial oxygenation, and cardiac work was higher over a wider range of perfusate Po2. In summary, heart mitochondria are limited by oxygen delivery with KH; supplementation of KH with PFC reverses mitochondrial hypoxia and improves cardiac performance, creating a more physiological tissue oxygen delivery. NEW & NOTEWORTHY Optical absorbance spectroscopy of intrinsic chromophores reveals that the commonly used crystalloid-perfused working heart is oxygen limited for oxidative phosphorylation and associated cardiac work. Oxygen-carrying perfluorocarbons increase myocardial oxygen delivery and improve cardiac function, providing a more physiological mitochondrial redox state and emphasizing cardiac work is modulated by myocardial oxygen delivery.

Burn State of the Science: Fluid Resuscitation.

Recognition of fluid creep has driven a large amount of the scientific investigation in the area of acute fluid resuscitation for burn patients. The role of colloids in ameliorating fluid creep is controversial, despite the fact that a fluid-sparing effect of colloids has been recognized for some time. All but one of the available prospective studies using colloids are more than a decade old, and a modern randomized controlled trial (RCT) comparing crystalloids to colloids is long overdue. While urinary output continues to be the main endpoint for fluid titration, there has been a moderate amount of interest in the use of transpulmonary thermodilution to guide fluid resuscitation. The available studies have found that transpulmonary thermodilution has had an inconsistent effect on limiting fluid resuscitation volumes and improving clinical outcomes. Computerized Decision Support Systems show great promise in optimizing fluid titration and reducing fluid resuscitation volumes, and an RCT comparing Computerized Decision Support Systems with conventional titration approaches will be the important next step. Use of high-dose vitamin C (ascorbic acid) has become a popular approach to limit fluid resuscitation volumes and edema formation, but it has been investigated in only two clinical studies: one a pseudo-randomized prospective study and the other a retrospective study. Improvements in clinical outcome have not been convincingly demonstrated, and concerns persist surrounding the possibility of induction of an osmotic diuresis, leading to intravascular volume depletion. An RCT is urgently required to evaluate high-dose vitamin C as an adjunct to crystalloid resuscitation compared with the use of crystalloids alone.

N-Acetylcysteine and Desferoxamine Reduce Pulmonary Oxidative Stress Caused by Hemorrhagic Shock in a Porcine Model.

AIM OF THE STUDY: To investigate the pulmonary oxidative stress and possible protective effect of N-Acetylcysteine (NAC) and Desferoxamine (DFX)in a porcine model subjected to hemorrhagic shock. MATERIALS AND METHODS: Twenty-one pigs were randomly allocated to Group-A (sham, n = 5), Group-B (fluid resuscitation, n = 8) and Group-C (fluid, NAC and DFX resuscitation, n = 8). Groups B and C were subjected to a 40-min shock period induced by liver trauma, followed by a 60-min resuscitation period. During shock, the mean arterial pressure (MAP) was maintained at 30-40 mmHg. Resuscitation consisted of crystalloids (35 mL/kg) and colloids (18 mL/kg) targeting to MAP normalization (baseline values ± 10%). In addition, Group-C received pretreatment with NAC 200 mg/kg plus DFX 2 g as intravenous infusions. Thiobarbituric Acid Reactive Substances (TBARS), protein carbonyls and glutathione peroxidase (GPx) activity were determined in lung tissue homogenates. Also, histological examination of pulmonary tissue specimens was performed. RESULTS: TBARS were higher in Group-B than in Group-A or Group-C: 2.90 ± 0.47, 0.57 ± 0.10, 1.78 ± 0.47 pmol/µg protein, respectively (p < 0.05). Protein carbonyls content was higher in Group-B than in Group-A or Group-C: 3.22 ± 0.68, 0.89 ± 0.30, 1.95 ± 0.54 nmol/mg protein, respectively (p > 0.05). GPx activity did not differ significantly between the three groups (p > 0.05). Lung histology was improved in Group-C versus Group-B, with less alveolar collapse, interstitial edema and inflammation. CONCLUSION: NAC plus DFX prevented the increase of pulmonary oxidative stress markers and protein damage after resuscitated hemorrhagic shock and had beneficial effect on lung histology. NAC/DFX combination may be used in the multimodal treatment of hemorrhagic shock, since it may significantly prevent free radical injury in the lung.

Effect of saline 0.9% or Plasma-Lyte 148 therapy on feeding intolerance in patients receiving nasogastric enteral nutrition.

OBJECTIVE: To compare the effect of Plasma-Lyte (PL)-148 and saline 0.9% (saline) on gastrointestinal (GI) feeding intolerance in mechanically ventilated patients receiving nasogastric (NG) feeding in an intensive care unit. DESIGN AND SETTING: A single-centre pilot study, nested within a multicentre, double-blind, cluster-randomised, double-crossover trial, performed in a mixed medical and surgical ICU. PARTICIPANTS: All adult patients who required crystalloid fluid therapy as part of the 0.9% Saline versus Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy (SPLIT) trial, were expected to need mechanical ventilation for more than 48 hours and were receiving enteral nutrition exclusively by NG tube were eligible. We enrolled 69 patients and assigned 35 to PL-148 and 34 to saline. INTERVENTIONS: We randomly allocated saline or PL-148 for four alternating 7-week blocks, with staff blinded to the solution. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients with GI feeding intolerance, defined as high gastric residual volume (GRV), diarrhoea or vomiting while receiving NG feeding in the ICU. The proportions of patients with each of high GRV, diarrhoea and vomiting were secondary outcomes. RESULTS: In the PL-148 group, 21 of 35 patients (60.0%) developed GI feeding intolerance, compared with 22 of 34 patients (64.7%) in the saline group (odds ratio [OR], 0.82; 95% CI, 0.31-2.17; P = 0.69). A high GRV was seen in four of 35 patients (11.4%) in the PL-148 group, and in 11 of 34 patients (32.4%) in the saline group (OR, 0.27; 95% CI, 0.08-0.96; P = 0.04). CONCLUSION: Among mechanically ventilated patients receiving NG feeding, the use of PL-148, compared with saline, did not reduce the proportion of patients developing GI feeding intolerance, but was associated with a decreased incidence of high GRV.

Preventing deaths due to haemorrhage.

Prevention of deaths from obstetric haemorrhage requires effective health systems including family planning, commodities, personnel, infrastructure and ultimately universal access to comprehensive obstetric care for women giving birth. The main causes of death associated with antepartum haemorrhage are placental abruption, placenta praevia and uterine rupture. Preventive measures include preconceptual folate supplementation, management of hypertensive disorders, early diagnosis of placenta praevia and use of uterine stimulants cautiously, particularly misoprostol. Preventive measures for post-partum haemorrhage include routine active management of the third stage of labour. Treatment involves a cascade of increasingly invasive interventions in rapid sequence until the bleeding is stopped. These interventions include fluid resuscitation, removal of the placenta, bimanual uterine compression, uterotonics, tranexamic acid, suturing of lower genital tract injury, blood product replacement, balloon tamponade, laparotomy, stepwise uterine devascularization, uterine compression sutures and hysterectomy. Emergency temporizing measures include application of the non-pneumatic anti-shock garment, and at laparotomy, aortic compression and uterine tourniquet application. The effectiveness of treatment methods and the optimal dosage of misoprostol are research priorities. Interesting new approaches include transvaginal uterine artery clamping and suction uterine tamponade.

Accuracy of potassium supplementation of fluids administered intravenously.

BACKGROUND: Potassium (K+) supplementation of isotonic crystalloid fluids in daily fluid therapy is commonly performed, yet its accuracy in veterinary medicine is undetermined. OBJECTIVE: To investigate the accuracy of K+ supplementation in isotonic crystalloid fluids. ANIMALS: None. METHODS: Observational study. 210 bags of fluid supplemented with KCl being administered to hospitalized dogs and cats intravenously (IV) were sampled over a 3-month period. Measured K+ concentration ([K+]) was compared to the intended [K+] of the bag. In a second experiment, 60 stock fluid bags were supplemented to achieve a concentration of 20 mmol/L K+, mixed well and [K+] was measured. In another 12 bags of 0.9% NaCl, K+ was added without mixing the bag, and [K+ ] of the delivered fluid was measured at regular time points during constant rate infusion. RESULTS: The measured [K+] was significantly higher than intended [K+] (mean difference 9.0 mmol/L, range 6.5 to >280 mmol/L, P < .0001). In 28% of clinical samples measured [K+] was ≥5 mmol/L different than intended [K+]. With adequate mixing, K+ supplementation of fluids can be accurate with the mean difference between measured and intended [K+] of 0.7 (95% CI -0.32 to 1.7) mmol/L. When not mixed, K(+) supplementation of 20 mmol/L can lead to very high [K+] of delivered fluid (up to 1410 mmol/L). CONCLUSIONS AND CLINICAL IMPORTANCE: Inadequate mixing following K+ supplementation of fluid bags can lead to potentially life threatening IV infused [K+]. Standard protocols for K+ supplementation should be established to ensure adequate mixing.

Acute atrial stretch results in conduction slowing and complex signals at the pulmonary vein to left atrial junction: insights into the mechanism of pulmonary vein arrhythmogenesis.

BACKGROUND: The pulmonary vein-left atrial (PV-LA) junction is key in pathogenesis of AF, and acute stretch is an important stimulus to AF. We aimed to characterize the response of the junction to acute stretch, hypothesizing that stretch would result in electrophysiological changes predisposing to re-entry. METHODS AND RESULTS: Fifteen participants undergoing cardiac surgery underwent evaluation of the right superior PV-LA junction using an epicardial mapping plaque. In 10, this was performed before and after atrial stretch imposed by rapid volume expansion, and in 5, it was performed with an intervening observation period. Activation was characterized by conduction slowing and electrogram fractionation transversely across the PV-LA junction, with lines of block also demonstrated perpendicular to the junction. Conduction was decremental (plaque activation time 135.8 ± 46.8 ms with programmed extra stimuli at 10 ms above effective refractory period versus 66.1 ± 22.9 ms with pacing at 400 ms; P<0.001) and percentage fractionation was greater with programmed extra stimuli at 10 ms above (33.5%± 15.3% versus 20.7%± 14.0%, P=0.001). Right atrial pressure increased by 2.5 ± 1.8 mm Hg (P=0.002) with volume expansion. Stretch resulted in conduction slowing across the PV-LA junction (increase in activation time 10.9 ± 14.6 ms in acute stretch group versus -0.1 ± 4.5 ms in control group; P=0.002). Conduction slowing was more marked with programmed extra stimuli at 10 ms above effective refractory period than with stable pacing (13.4 ± 16.5 ms versus 1.7 ± 5.4 ms; P=0.003). Stretch resulted in a significant increase in fractionated electrograms (7.9%± 7.0% versus -0.4 ± 3.3; P=0.004). CONCLUSIONS: Acute stretch results in conduction slowing across the PV-LA junction, with a greater degree of signal complexity. This substrate may be important in AF initiation and maintenance by promoting re-entry.

Effects of intravenous solutions on acid-base equilibrium: from crystalloids to colloids and blood components.

Intravenous fluid administration is a medical intervention performed worldwide on a daily basis. Nevertheless, only a few physicians are aware of the characteristics of intravenous fluids and their possible effects on plasma acid-base equilibrium. According to Stewart's theory, pH is independently regulated by three variables: partial pressure of carbon dioxide, strong ion difference (SID), and total amount of weak acids (ATOT). When fluids are infused, plasma SID and ATOT tend toward the SID and ATOT of the administered fluid. Depending on their composition, fluids can therefore lower, increase, or leave pH unchanged. As a general rule, crystalloids having a SID greater than plasma bicarbonate concentration (HCO3-) cause an increase in plasma pH (alkalosis), those having a SID lower than HCO3- cause a decrease in plasma pH (acidosis), while crystalloids with a SID equal to HCO3- leave pH unchanged, regardless of the extent of the dilution. Colloids and blood components are composed of a crystalloid solution as solvent, and the abovementioned rules partially hold true also for these fluids. The scenario is however complicated by the possible presence of weak anions (albumin, phosphates and gelatins) and their effect on plasma pH. The present manuscript summarises the characteristics of crystalloids, colloids, buffer solutions and blood components and reviews their effect on acid-base equilibrium. Understanding the composition of intravenous fluids, along with the application of simple physicochemical rules best described by Stewart's approach, are pivotal steps to fully elucidate and predict alterations of plasma acid-base equilibrium induced by fluid therapy.

Molecular size and origin do not influence the harmful side effects of hydroxyethyl starch on human proximal tubule cells (HK-2) in vitro.

BACKGROUND: Recently, clinical trials revealed renal impairment induced by hydroxyethyl starch (HES) in septic patients. In prior studies, we managed to demonstrate that HES accumulated in renal proximal tubule cells (PTCs). The related pathomechanism has not yet been discovered. To validate our hypothesis that the HES molecule itself is harmful, regardless of its molecule size or origin, we conducted a comprehensive study to elucidate the influences of different HES preparations on PTC viability in vitro. METHODS: Cell viability of human PTC was measured with a cytotoxicity assay, quantifying the reduction of tetrazolium salt to colored formazan. Experiments were performed by assessing the influence of different carrier solutions of HES (balanced, nonbalanced, culture medium), different average molecular weights (70, 130, 200 kDa), different origins (potato or corn derived), and various durations of incubation (2-21 hours). Furthermore, HES 130/0.4 was fractionated by ultrafiltration, and the impact on cell viability of average single-size fractions with <3, 3 to 10, 10 to 30, 30 to 50, 50 to 100, and >100 kDa was investigated. We also tested the possible synergistic effects of inflammation induced by tumor necrosis factor-α. RESULTS: All tested HES solutions, regardless of origin or carrier matrix, decreased cell viability in an equivalent, dose-dependent manner. Coincubation with tumor necrosis factor-α did not reduce HES-induced reduction of cell viability. Minor differences were detected comparing 70, 130, and 200 kDa preparations. Analysis of fractionated HES revealed that each fraction decreased cell viability. Even small HES molecules (10-30 kDa) were significantly deleterious. CONCLUSIONS: For the first time, we were able to show that only the total mass of HES molecules applied is responsible for the harmful impact on renal PTC in vitro. Neither molecular size nor their origin showed any relevance.