Osmoprotection in Salvia hispanica L seeds under water stress attenuators / Osmoproteção em sementes de Salvia hispanica L sob atenuadores do estresse hídrico

Salvia hispanica cultivation is recent in Brazil and occurs in the off-season, when there is lower water availability in the soil. Water deficit is one of the abiotic factors that most limit germination for compromising the sequence of metabolic events that culminate with seedling emergence. Several attenuating substances have been used to mitigate the effects resulting from this stress and give higher tolerance to the species. Thus, the objective of this study was to evaluate the action of different agents as water stress attenuators in the germination and accumulation of organic compounds in S. hispanica seedlings. The treatments consisted of pre-soaking the seeds for 4 hours in salicylic acid (1 mM.L-¹), gibberellic acid (0.4 mM.L-¹), distilled water and control treatment (without soaking). The seeds were germinated at osmotic potentials of 0.0, -0.1, -0.2, -0.3 and -0.4 MPa, using PEG 6000 as an osmotic agent. The variables germination percentage, germination speed index, shoot and primary root lengths, total dry mass, proline, total soluble sugars and total free amino acids were analyzed. Salicylic acid and gibberellic acid led to the best results among the attenuators tested, increasing germination, length, dry mass and biochemical components of S. hispanica seedlings under water deficit. Therefore, salicylic and gibberellic acids are efficient in mitigating water stress in S. hispanica seeds up to the potential of -0.4 MPa.

O cultivo da Salvia hispanica é recente no Brasil e se dá no período de entressafra, quando há menor disponibilidade hídrica no solo. O déficit hídrico é um dos fatores abióticos que mais limitam a germinação por comprometer a sequência de eventos metabólicos que culminam com a emergência da plântula. Diversas substâncias atenuadoras têm sido empregadas com a finalidade de mitigar os efeitos resultantes desse estresse e conferir maior tolerância às espécies. Desse modo, objetivou-se avaliar a ação de diferentes agentes como atenuadores do estresse hídrico na germinação e acúmulo de compostos orgânicos em plântulas de S. hispanica. Os tratamentos consistiram na pré-embebição das sementes durante 4 horas em ácido salicílico (1 mM.L-¹), ácido giberélico (0,4 mM.L-¹), água destilada e o tratamento controle (sem embebição). As sementes foram germinadas sob os potenciais osmóticos 0,0, -0,1, -0,2, -0,3 e -0,4 MPa, utilizando PEG 6000 como agente osmótico. Analisaram-se as variáveis porcentagem de germinação, índice de velocidade de germinação, comprimento da parte aérea e da raiz primária, massa seca total, prolina, açúcares solúveis totais e aminoácidos livres totais. O ácido salicílico e o ácido giberélico apresentaram os melhores resultados, dentre os atenuadores testados, incrementando a germinação, o comprimento, a massa seca e os componentes bioquímicos de plântulas de S. hispanica sob déficit hídrico. Logo, os ácidos salicílico e giberélico são eficientes na mitigação do estresse hídrico em sementes de S. hispanica até o potencial -0,4 MPa.

Carbohydrate hastens hypervolemia achieved through ingestion of aqueous sodium solution in resting euhydrated humans.

PURPOSE: Ingesting beverages containing a high concentration of sodium under euhydrated conditions induces hypervolemia. Because carbohydrate can enhance interstitial fluid absorption via the sodium-glucose cotransporter and insulin-dependent renal sodium reabsorption, adding carbohydrate to high-sodium beverages may augment the hypervolemic response. METHODS: To test this hypothesis, we had nine healthy young males ingest 1087 ± 82 mL (16-17 mL per kg body weight) of water or aqueous solution containing 0.7% NaCl, 0.7% NaCl + 6% dextrin, 0.9% NaCl, or 0.9% NaCl + 6% dextrin under euhydrated conditions. Each drink was divided into six equal volumes and ingested at 10-min intervals. During each trial, participants remained resting for 150 min. Measurements were made at baseline and every 30 min thereafter. RESULTS: Plasma osmolality decreased with water ingestion (P ≤ 0.023), which increased urine volume such that there was no elevation in plasma volume from baseline (P ≥ 0.059). The reduction in plasma osmolality did not occur with ingestion of solution containing 0.7% or 0.9% NaCl (P ≥ 0.051). Consequently, urine volume was 176-288 mL smaller than after water ingestion and resulted in plasma volume expansion at 60 min and later times (P ≤ 0.042). In addition, net fluid balance was 211-329 mL greater than after water ingestion (P ≤ 0.028). Adding 6% dextrin to 0.7% or 0.9% NaCl solution resulted in plasma volume expansion within as little as 30 min (P ≤ 0.026), though the magnitudes of the increases in plasma volume were unaffected (P ≥ 0.148). CONCLUSION: Dextrin mediates an earlier hypervolemic response associated with ingestion of high-sodium solution in resting euhydrated young men. (247/250 words).

Can an amino acid mixture alleviate gastrointestinal symptoms in neuroendocrine tumor patients?

BACKGROUND: Neuroendocrine tumors, although relatively rare in incidence, are now the second most prevalent gastrointestinal neoplasm owing to indolent disease biology. A small but significant sub-group of neuroendocrine tumor patients suffer from diarrhea. This is usually secondary to carcinoid syndrome but can also be a result of short gut syndrome, bile acid excess or iatrogenic etiologies. Recently, an amino acid based oral rehydration solution (enterade® Advanced Oncology Formula) was found to have anti-diarrheal properties in preclinical models. METHODS: A retrospective chart review of all NET patients treated with enterade® AO was performed after IRB approval. RESULTS: Ninety-eight NET patients who had received enterade® AO at our clinic from May 2017 through June 2019 were included. Patients (N = 49 of 98) with follow up data on bowel movements (BMs) were included for final analysis. Eighty-four percent of patients (41/49) had fewer BMs after taking enterade® AO and 66% (27/41) reported more than 50% reduction in BM frequency. The mean number of daily BMs was 6.6 (range, 3-20) at baseline before initiation of therapy, while the mean number of BMs at 1 week time point post enterade® AO was 2.9 (range, 0-11). CONCLUSIONS: Our retrospective observations are encouraging and support prospective validation with appropriate controls in NET patients. This is first published report of the potential anti-diarrheal activity of enterade® AO in NET patients.

Strong community-based health systems and national governance predict improvement in coverage of oral rehydration solution (ORS): a multilevel longitudinal model.

Diarrheal disease remains a leading cause of child death globally, especially in low and middle-income countries. Use of oral rehydration solution (ORS) for treatment of diarrhea in children, a very cost-effective intervention, remains below 50% in many countries. Here we use a multi-level longitudinal model to reveal important predictors of ORS use at the national level. The findings suggest that increasing government effectiveness along with increased implementation and affordability of community-based health programs can lead to substantial increases in ORS use. Key informant interviews with national health leaders in countries that significantly improved ORS coverage support these quantitative findings.

Can an amino acid-based oral rehydration solution be effective in managing immune therapy-induced diarrhea?

Immune checkpoint inhibitor (ICPi) therapy has transformed the way we treat cancer. However, its immune related adverse events (irAEs) can be debilitating and life threatening. Immune therapy-induced diarrhea (ITID) is one of the most commonly encountered irAEs and can lead to expensive and prolonged hospitalizations. The current standard of care for grade 3 or 4 ITID involves ICPi discontinuation, the initiation of steroids, and infliximab for refractory disease. This treatment regimen reverses the desired anti-tumor effect of ICPis, can lead to side effects, and is cost-ineffective. We report the first case of the successful treatment of grade 3 ITID with steroids and an amino acid-based oral rehydration solution (AA-ORS), enterade. Research suggests that AA-ORS may be used to reduce diarrhea and adequately hydrate patients, in contrast to glucose-based oral rehydration solutions, which have been implicated as a contributing factor to diarrhea in cancer patients. We hypothesize that an AA-ORS may mitigate ITID via safer and more economically viable means than the current standard of care, but more controlled trials are needed to test this hypothesis.

Impact of Capnoperitoneum on Renal Perfusion and Urine Production in Infant and Adolescent Pigs: Crystalloid versus Colloid Fluid Resuscitation.

BACKGROUND: Infants are likely to develop anuria during laparoscopy which is uncommon in older patients. The reason for this susceptibility remains unknown. We compared the impact of CO2 pneumoperitoneum on renal perfusion and urine production in piglets compared with adolescent pigs. We furthermore investigated the effects of different resuscitation strategies. MATERIALS AND METHODS: Male piglets (n = 21) were divided into four groups: (a) infant controls (n = 5), (b) infants with crystalloid restitution (n = 6), (c) infants with colloidal restitution (n = 5), and (d) adolescents with crystalloid restitution (n = 5). Animals were ventilated, the central vessels and ureters were cannulated, and the animals were subjected to a 3-hour, 10 mm Hg CO2 pneumoperitoneum followed by 2-hour resuscitation. Renal perfusion was assessed by fluorescent microspheres and the rate of urine flow was measured. RESULTS: Urine production significantly decreased after insufflation only in the infant crystalloid and adolescent group, but not in controls or infants treated with colloids. In the infant crystalloid group, urine production remained at levels below 20% of baseline throughout the experiment. In this group, the renal perfusion dropped significantly after the beginning of the capnoperitoneum and remained significantly reduced throughout the experiment. CONCLUSION: Our data indicates that capnoperitoneum impairs renal perfusion and urine production in infants. In moderate-pressure capnoperitoneum, this effect cannot be compensated by application of crystalloids but with colloids.

Primary Hyperparathyroidism in Pregnancy: Maternofetal Outcomes at a Quaternary Referral Obstetric Hospital, 2000 Through 2015.

Context: Primary hyperparathyroidism (PHPT) in pregnancy has historically been associated with substantial maternofetal morbidity and mortality rates. The optimal treatment and timing of surgical intervention in pregnancy remain contested. Objective: To compare maternofetal outcomes of medically and surgically treated patients with PHPT in pregnancy. Design: Retrospective chart review. Setting: Quaternary referral hospital. Patients: Women with PHPT in pregnancy treated between 1 January 2000 and 31 December 2015. Interventions: Medical therapy or parathyroid surgery. Main Outcomes Measured: Timing of diagnosis; maternal corrected serum calcium concentrations; gestation, indication and mode of delivery; complications attributable to PHPT; birth weight; and admission to the neonatal intensive care unit (NICU). Results: Twenty-two pregnancies were managed medically, and six patients underwent parathyroidectomy in pregnancy (five in trimester 2, and one at 32 weeks gestation). Most patients treated medically either had a corrected serum calcium concentration <2.85 mmol/L in early pregnancy or had PHPT diagnosed in trimester 3. Of viable medically managed pregnancies, 30% were complicated by preeclampsia, and preterm delivery occurred in 66% of this group. All preterm neonates required admission to the NICU for complications related to prematurity. All surgically treated patients delivered their babies at term, and there were no complications of parathyroid surgery. Conclusion: Maternofetal outcomes have improved relative to that reported in early medical literature in patients treated medically and surgically, but the rates of preeclampsia and preterm delivery were higher in medically treated patients. The study was limited by its retrospective design and small sample sizes.

Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery.

BACKGROUND: Guidelines to promote the early recovery of patients undergoing major surgery recommend a restrictive intravenous-fluid strategy for abdominal surgery. However, the supporting evidence is limited, and there is concern about impaired organ perfusion. METHODS: In a pragmatic, international trial, we randomly assigned 3000 patients who had an increased risk of complications while undergoing major abdominal surgery to receive a restrictive or liberal intravenous-fluid regimen during and up to 24 hours after surgery. The primary outcome was disability-free survival at 1 year. Key secondary outcomes were acute kidney injury at 30 days, renal-replacement therapy at 90 days, and a composite of septic complications, surgical-site infection, or death. RESULTS: During and up to 24 hours after surgery, 1490 patients in the restrictive fluid group had a median intravenous-fluid intake of 3.7 liters (interquartile range, 2.9 to 4.9), as compared with 6.1 liters (interquartile range, 5.0 to 7.4) in 1493 patients in the liberal fluid group (P<0.001). The rate of disability-free survival at 1 year was 81.9% in the restrictive fluid group and 82.3% in the liberal fluid group (hazard ratio for death or disability, 1.05; 95% confidence interval, 0.88 to 1.24; P=0.61). The rate of acute kidney injury was 8.6% in the restrictive fluid group and 5.0% in the liberal fluid group (P<0.001). The rate of septic complications or death was 21.8% in the restrictive fluid group and 19.8% in the liberal fluid group (P=0.19); rates of surgical-site infection (16.5% vs. 13.6%, P=0.02) and renal-replacement therapy (0.9% vs. 0.3%, P=0.048) were higher in the restrictive fluid group, but the between-group difference was not significant after adjustment for multiple testing. CONCLUSIONS: Among patients at increased risk for complications during major abdominal surgery, a restrictive fluid regimen was not associated with a higher rate of disability-free survival than a liberal fluid regimen and was associated with a higher rate of acute kidney injury. (Funded by the Australian National Health and Medical Research Council and others; RELIEF ClinicalTrials.gov number, NCT01424150 .).

Shortened Preoperative Fasting Time to Allow Oral Rehydration Solution Clear Liquid up to Two Hours before Elective Major Surgery in Adults.

OBJECTIVE: To generate evidence of feasibility to allow clear liquid 2 hours before elective surgery. STUDY DESIGN: Cross-sectional observational study. PLACE AND DURATION OF STUDY: The Department of Surgery, Patan Hospital, Patan Academy of Health Sciences, Nepal, from October to December 2016. METHODOLOGY: One hundred consecutive adult elective major surgery patients of American Society of Anesthesiologist criteria 1 or 2 were enrolled. The protocol was discussed with patients, nurses, anesthetists and surgeons to allow 500 ml clear liquid (ORS) up to 0600 hours on the day of surgery to maintain minimum of 2 hours (h) nil per os (NPO) before surgery. Compliance, discomfort, nausea and vomiting were observed. Institutional review committee approved the study. Microsoft excel was used for descriptive analysis. RESULTS: All 100 patients completed the protocol of shortened fasting time. Two patients had incomplete records and were excluded from analysis. Among the 98 patients analysed, age was 48 ±12.38 years with 74 females (75.51% of 98). There were 68 gastrointestinal, 20 urosurgery and 10 others surgeries. There was no discomfort, nausea or vomiting reported due to ORS 2-h before elective surgery. CONCLUSION: Preoperative clear liquid up to 2-h before elective surgery in adults is feasible and safe in our set-up to shorten the fasting time.

HYDration and Bicarbonate to Prevent Acute Renal Injury After Endovascular Aneurysm Repair With Suprarenal Fixation: Pilot/Feasibility Randomised Controlled Study (HYDRA Pilot Trial).

OBJECTIVE/BACKGROUND: Up to 25% of patients undergoing elective endovascular aneurysm repair (EVAR) develop acute kidney injury (AKI), which is associated with short and long-term morbidity and mortality. There is no high quality randomised evidence regarding prevention of EVAR related AKI. METHODS: A novel AKI prevention strategy for EVAR was devised, based on best evidence and an expert consensus group. This included a bolus of high dose sodium bicarbonate (NaHCO3) immediately before EVAR (1 mL/kg of 8.4% NaHCO3) and standardised crystalloid based hydration pre- and post-EVAR. A pilot/feasibility randomised controlled trial (RCT) was performed in two centres to assess the safety of the intervention, potential impact on AKI prevention, and feasibility of a national RCT; the primary end point was the proportion of eligible patients recruited into the study. AKI was defined using "Kidney Disease Improving Global Outcomes" and "Acute Kidney Injury Network" criteria based on National Institute for Health and Clinical Excellence AKI recommendations, using serum creatinine and hourly urine output. RESULTS: Fifty-eight patients (84% of those screened; median age 75 years [range 57-89 years], 10% female) were randomised to receive the standardised intravenous hydration with (intervention) or without (control) NaHCO3. Groups were comparable in terms of AKI risk factors; 56 of 58 participants had a device with suprarenal fixation. Overall, 33% of patients in the control arm developed AKI versus 7% in the intervention arm (as treated analysis). None of the patients receiving NaHCO3 developed a serious intervention related adverse event; five patients did not attend their 30 day follow-up. CONCLUSION: Bolus high dose NaHCO3 and hydration is a promising EVAR related AKI prevention method. This trial has confirmed the feasibility of delivering a definitive large RCT to confirm the efficacy of this novel intervention, in preventing EVAR related AKI.

Effects of Intraoperative Fluid Management on Postoperative Outcomes: A Hospital Registry Study.

OBJECTIVE: Evaluate the dose-response relationship between intraoperative fluid administration and postoperative outcomes in a large cohort of surgical patients. BACKGROUND: Healthy humans may live in a state of fluid responsiveness without the need for fluid supplementation. Goal-directed protocols driven by such measures are limited in their ability to define the optimal fluid state during surgery. METHODS: This analysis of data on file included 92,094 adult patients undergoing noncardiac surgery with endotracheal intubation between 2007 and 2014 at an academic tertiary care hospital and two affiliated community hospitals. The primary exposure variable was total intraoperative volume of crystalloid and colloid administered. The primary outcome was 30-day survival. Secondary outcomes were respiratory complications within three postoperative days (pulmonary edema, reintubation, pneumonia, or respiratory failure) and acute kidney injury. Exploratory outcomes were postoperative length of stay and total cost of care. Our models were adjusted for patient-, procedure-, and anesthesia-related factors. RESULTS: A U-shaped association was observed between the volume of fluid administered intraoperatively and 30-day mortality, costs, and postoperative length of stay. Liberal fluid volumes (highest quintile of fluid administration practice) were significantly associated with respiratory complications whereas both liberal and restrictive (lowest quintile) volumes were significantly associated with acute kidney injury. Moderately restrictive volumes (second quintile) were consistently associated with optimal postoperative outcomes and were characterized by volumes approximately 40% less than traditional textbook estimates: infusion rates of approximately 6-7 mL/kg/hr or 1 L of fluid for a 3-hour case. CONCLUSIONS: Intraoperative fluid dosing at the liberal and restrictive margins of observed practice is associated with increased morbidity, mortality, cost, and length of stay.

Comparison of Postoperative Pain and Residual Gas Between Restrictive and Liberal Fluid Therapy in Patients Undergoing Laparoscopic Cholecystectomy.

BACKGROUND: Different fluid regimens are used in the clinical management of perioperative fluid therapy, but there still is the argument about which fluid regimen is better for patients. This study was mainly designed to compare different fluid regimens on postoperative pain and residual gas in patients undergoing laparoscopic cholecystectomy. METHODS: A total of 100 patients were equally randomized to receive restrictive fluid infusion (n=50) with lactated Ringer (LR) solution 5 mL/kg/h or liberal fluid infusion (n=50), with 30 mL/kg/h lactated Ringer solution. Postoperative pain was evaluated at 1, 6, and 24 hours after surgery using a visual analog scale (VAS). Postoperative subdiaphragmatic residual gas was monitored by x-ray at 24 hours after surgery. RESULTS: Patients in the restrictive group had significantly higher VAS pain scores at 6 hours after surgery than those in the liberal group (P=0.009). The incidence of subdiaphragmatic residual gas in the restrictive group was higher than in the liberal group (P=0.045). Patients who had residual gas had higher VAS pain scores than those with no residual gas in the restrictive group at 6 hours after surgery (P=0.02). CONCLUSIONS: Patients undergoing laparoscopic cholecystectomy with restrictive fluid therapy may suffer more severe postoperative pain than those receiving liberal fluid therapy. It suggests that the higher incidence of subdiaphragmatic residual gas may have occurred with restrictive fluid therapy.

Crystalloid versus colloid fluids for reduction of postoperative ileus after abdominal operation under combined general and epidural anesthesia.

BACKGROUND: The main objective of this study was to compare the effect of perioperative administration of crystalloid versus colloid solutions and its impact on reversal of ileus after resection with primary anastomosis of intestine. We hypothesized that inclusion of colloids will improve the return of intestinal motility. METHODS: In a double-blinded clinical trial, 91 the American Society of Anesthesiologists I to III patients undergoing abdominal operation for resection with anastomosis of small or large intestine were randomized to receive either lactated Ringer solution crystalloid group or 6% hydroxyethyl starch colloid group to replace intraoperative fluid loss (blood loss + third space). The time to resume normal intestinal motility was the primary end point and the prevalence of composite postoperative complications was the secondary end point. RESULTS: Average duration of ileus was 86.7 ± 23.6 hours in crystalloid group and it lasted 73.4 ± 20.8 hours in colloid group (P = .006). While there was no difference in the frequency of postoperative nausea and vomiting between the 2 groups (P = .3), the actual vomiting occurred less frequently in colloid group (P = .02). Serum concentrations of potassium ion decreased significantly in both groups, whereas the degree of potassium changes was more remarkable in colloid group compared with crystalloid group (P = .03). Postoperative ileus did not correlate with sex, age, and the duration of operation. Duration of hospital stay was similar between the 2 groups. CONCLUSION: We concluded that administration of colloids as a part of perioperative fluid management improves intestinal motility and shortens the duration of ileus after gastrointestinal operations. This may improve the tolerance for enteral feeding and reduce ileus-related symptoms.

Arterial Pressure and the Rate of Elimination of Crystalloid Fluid.

Excretion of crystalloid fluid is slow during general anesthesia. The distribution and elimination of buffered Ringer's solution were analyzed to determine whether the rate of elimination correlates with a hemodynamic factor, consciousness, patient posture, or the type of general anesthesia. Data were derived from 4 separately published studies in which 30 volunteers and 48 anesthetized patients had received 0.833 (1 series 0.667) mL/kg/min of lactated or acetated Ringer's solution over 30 minutes. Frequent measurements of the blood hemoglobin and mean urinary excretion were used as input in a kinetic analysis according to a 2-volume model and covariates, using microconstants and mixed-effects modeling software.The results show that rate of elimination of crystalloid fluid decreased with the mean arterial pressure (MAP) and patient age, but was unaffected by consciousness and inhalational or intravenous anesthesia. The elimination rate constant was 6.5 (95% confidence interval, 5.2-7.9) × 10 × (MAP/mean MAP) × (Age/mean Age). The mean MAP for the 2108 data points was 81.3 mm Hg and the mean age was 40 years. The central fluid space that was expanded by infused fluid (Vc, plasma volume) increased with body weight but decreased with general anesthesia and with reductions of MAP.Simulations revealed a more than 10-fold difference in the excreted fluid volume after a theoretical 30-minute infusion, depending on whether the MAP was 50 or 100 mm Hg.In conclusion, the rate of elimination of crystalloid fluid decreased in proportion to MAP but was independent of general anesthesia and moderate-sized surgery.

Gastric Fluid Volume Change After Oral Rehydration Solution Intake in Morbidly Obese and Normal Controls: A Magnetic Resonance Imaging-Based Analysis.

BACKGROUND: Although preoperative fluid intake 2 hours before anesthesia is generally considered safe, there are concerns about delayed gastric emptying in obese subjects. In this study, the gastric fluid volume (GFV) change in morbidly obese subjects was investigated after ingesting an oral rehydration solution (ORS) and then compared with that in nonobese subjects. METHODS: GFV change over time after the ingestion of 500 mL of ORS containing 2.5% carbohydrate (OS-1) was measured in 10 morbidly obese subjects (body mass index [BMI], >35) scheduled for bariatric surgery and 10 nonobese (BMI, 19-24) using magnetic resonance imaging. After 9 hours of fasting, magnetic resonance imaging scans were performed at preingestion, 0 min (just after ingestion), and every 30 minutes up to 120 minutes. GFV values were compared between morbidly obese and control groups and also between preingestion and postingestion time points. RESULTS: The morbidly obese group had a significantly higher body weight and BMI than the control group (mean body weight and BMI in morbidly obese, 129.6 kg and 46.3 kg/m, respectively; control, 59.5 kg and 21.6 kg/m, respectively). GFV was significantly higher in the morbidly obese subjects compared with the control group at preingestion (73 ± 30.8 mL vs 31 ± 19.9 mL, P = .001) and at 0 minutes after ingestion (561 ± 30.8 mL vs 486 ± 42.8 mL; P < .001). GFV declined rapidly in both groups and reached fasting baseline levels by 120 minutes (morbidly obese, 50 ± 29.5 mL; control, 30 ± 11.6 mL). A significant correlation was observed between preingestion residual GFV and body weight (r = .66; P = .001). CONCLUSIONS: Morbidly obese subjects have a higher residual gastric volume after 9 hours of fasting compared with subjects with a normal BMI. However, no differences were observed in gastric emptying after ORS ingestion in the 2 populations, and GFVs reached baseline within 2 hours after ORS ingestion. Further studies are required to confirm whether the preoperative fasting and fluid management that are recommended for nonobese patients could also be applied to morbidly obese patients.

How and why are subcutaneous fluids administered in an advanced illness population: a systematic review.

AIMS AND OBJECTIVES: To identify the mechanisms of subcutaneous fluid administration in advanced illness. BACKGROUND: Hydration at end of life is a fundamental issue in quality care internationally. Decision-making regarding the provision of artificial hydration in advanced illness is complicated by a paucity of evidence-based guidance. Despite considerable attention given to the topic including two recent Cochrane reviews, there has been no focus in systematically identifying papers that report the mechanisms for delivering hydration subcutaneously. Consequently, there is a need to produce guidance on the site, mode, volume and rate of infusion, based on empirical evidence. DESIGN: Systematic review of papers reporting empirical research data. METHODS: Key databases (CENTRAL, Medline, EMBASE, Web of Science, CINAHL) were searched in September 2015, with no date limitations. Inclusion criteria focused on hypodermoclysis in adults within an advanced illness population. Selected studies were reviewed for quality and a risk-of-bias assessment was conducted for the included studies. RESULTS: Fourteen papers were included in the analysis; most (n = 8) were conducted in hospices with others (n = 6) in long-stay units with a population affected by chronic conditions associated with ageing. Studies were of moderate or high quality. The site and mode of infusion were not well described in these papers, and rates of infusion varied widely allowing for little clear consensus to guide clinical practice in the administration of subcutaneous fluids. CONCLUSIONS: Studies under-report the mechanisms by which artificial hydration is provided, creating a paucity of evidence-based guidance by which to practice. There is a need for evidence generated from nonmalignant populations to ensure applicability to the large number of people with other advanced illness. RELEVANCE TO CLINICAL PRACTICE: In the absence of sufficiently powered robust evidence, the mode of delivery of artificial hydration at end of life remains in the gloaming between evidence and unfounded habit.

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.

Hemodynamic Effect of Different Doses of Fluids for a Fluid Challenge: A Quasi-Randomized Controlled Study.

OBJECTIVE: The objectives of this study are to determine what is the minimal volume required to perform an effective fluid challenge and to investigate how different doses of IV fluids in an fluid challenge affect the changes in cardiac output and the proportion of responders and nonresponders. DESIGN: Quasi-randomized controlled trial. SETTING: Cardiothoracic ICU, tertiary university hospital. PATIENTS: Eighty postcardiac surgery patients. INTERVENTION: IV infusion of 1, 2, 3, or 4 mL/Kg (body weight) of crystalloid over 5 minutes. MEASUREMENTS AND MAIN RESULTS: Mean systemic filling pressure measured using the transient stop-flow arm arterial-venous equilibrium pressure, arterial and central venous pressure, cardiac output (LiDCOplus; LiDCO, Cambridge, United Kingdom), and heart rate. The groups were well matched with respect to demographic and baseline physiologic variables. The proportion of responders increased from 20% in the group of 1 mL/kg to 65% in the group of 4 mL/kg (p = 0.04). The predicted minimal volume required for an fluid challenge was between 321 and 509 mL. Only 4 mL/Kg increases transient stop-flow arm arterial-venous equilibrium pressure beyond the limits of precision and was significantly associated with a positive response (odds ratio, 7.73; 95% CI, 1.78-31.04). CONCLUSION: The doses of fluids used for an fluid challenge modify the proportions of responders in postoperative patients. A dose of 4 mL/Kg increases transient stop-flow arm arterial-venous equilibrium pressure and reliably detects responders and nonresponders.

Initial 12-h operative fluid volume is an independent risk factor for pleural effusion after hepatectomy.

Pleural effusion after hepatectomy is associated with significant morbidity and prolonged hospital stays. Several studies have addressed the risk factors for postoperative pleural effusion. However, there are no researches concerning the role of the initial 12-h operative fluid volume. The aim of this study was to evaluate whether the initial 12-h operative fluid volume during liver resection is an independent risk factor for pleural effusion after hepatectomy. In this study, we retrospectively analyzed clinical data of 470 patients consecutively undergoing elective hepatectomy between January 2011 and December 2012. We prospectively collected and retrospectively analyzed baseline and clinical data, including preoperative, intraoperative, and postoperative variables. Univariate and multivariate analyses were carried out to identify whether the initial 12-h operative fluid volume was an independent risk factor for pleural effusion after hepatectomy. The multivariate analysis identified 2 independent risk factors for pleural effusion: operative time [odds ratio (OR)=10.2] and initial 12-h operative fluid volume (OR=1.0003). Threshold effect analyses revealed that the initial 12 h operative fluid volume was positively correlated with the incidence of pleural effusion when the initial 12-h operative fluid volume exceeded 4636 mL. We conclude that the initial 12-h operative fluid volume during liver resection and operative time are independent risk factors for pleural effusion after hepatectomy. Perioperative intravenous fluids should be restricted properly.

Variation in crystalloid administration: an analysis of 6248 patients undergoing major elective surgery.

BACKGROUND: Large variations exist regarding the type and volume of fluid to be administered to patients. This study aimed to quantitate variations in the administration of crystalloid fluids at the level of the patient, provider, and procedure at a large, tertiary care center. METHOD: Patients who underwent major cardiac, thoracic, or abdominal procedures between 2011 and 2014 were identified. Variations in crystalloid administration were compared by procedure and provider using a coefficient of variation (CV). Multivariable hierarchical linear modeling was performed to identify factors predictive of fluid administration and quantitate variation at the level of the patient and provider. RESULTS: Among 6248 patients who met inclusion criteria, the average crystalloid volume was 25.8 mL kg(-1) m(2) h(-1), corresponding to a CV of 55%. Patients who underwent pancreatectomy received the highest corrected crystalloid volume (32.7 mL kg(-1) m(2) h(-1)), whereas those who underwent coronary artery bypass grafting received the lowest corrected crystalloid volume (14.7 mL kg(-1) m(2) h(-1)). Variations in fluid practices were noted between providers (corrected CV; 14.7%-97.1%) and within the practices of the same provider (corrected CV range; 24.1%-87.9%). On multivariable analysis, age and changes in hemoglobin concentration were associated with a higher crystalloid volume (both P < 0.05). Although over 90% of the variation was attributed to patient-level factors, approximately 10% was due to factors at level of the provider (surgeon: 5.8% versus anesthesiologist: 3.4%). CONCLUSIONS: Wide variations were noted in crystalloid administration between procedures, providers, and within providers. Evidence-based practices and goal-directed therapies should be incorporated to avoid unwanted variations.