Balanced Crystalloids Versus Normal Saline in Kidney Transplant Patients: An Updated Systematic Review, Meta-analysis, and Trial Sequential Analysis.

BACKGROUND: The use of balanced crystalloids over normal saline for perioperative fluid management during kidney transplantation and its benefits on acid-base and electrolyte balance along with its influence on postoperative clinical outcomes remains a topic of controversy. Therefore, we conducted this review to assess the impact of balanced solutions compared to normal saline on outcomes for kidney transplant patients. METHODS: We searched MEDLINE, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) comparing balanced lower-chloride solutions to normal saline in renal transplant patients. Our main outcome of interest was delayed graft function (DGF). Additionally, we examined acid-base and electrolyte measurements, along with postoperative renal function. We computed relative risk (RR) using the Mantel-Haenszel test for binary outcomes, and mean difference (MD) for continuous data, and applied DerSimonian and Laird random-effects models to address heterogeneity. Furthermore, we performed a trial sequential analysis (TSA) for all outcomes. RESULTS: Twelve RCTs comprising a total of 1668 patients were included; 832 (49.9%) were assigned to receive balanced solutions. Balanced crystalloids reduced the occurrence of DGF compared to normal saline, with RR of 0.82 (95% confidence interval [CI], 0.71-0.94), P = .005; I² = 0%. The occurrence was 25% (194 of 787) in the balanced crystalloids group and 34% (240 of 701) in the normal saline group. Moreover, our TSA supported the primary outcome result and suggests that the sample size was sufficient for our conclusion. End-of-surgery chloride (MD, -8.80 mEq·L -1 ; 95% CI, -13.98 to -3.63 mEq.L -1 ; P < .001), bicarbonate (MD, 2.12 mEq·L -1 ; 95% CI, 1.02-3.21 mEq·L -1 ; P < .001), pH (MD, 0.06; 95% CI, 0.04-0.07; P < .001), and base excess (BE) (MD, 2.41 mEq·L -1 ; 95% CI, 0.88-3.95 mEq·L -1 ; P = .002) significantly favored the balanced crystalloids groups and the end of surgery potassium (MD, -0.17 mEq·L -1 ; 95% CI, -0.36 to 0.02 mEq·L -1 ; P = .07) did not differ between groups. However, creatinine did not differ in the first (MD, -0.06 mg·dL -1 ; 95% CI, -0.38 to 0.26 mg·dL -1 ; P = .71) and seventh (MD, -0.06 mg·dL -1 ; 95% CI, -0.18 to 0.06 mg·dL -1 ; P = .30) postoperative days nor urine output in the first (MD, -1.12 L; 95% CI, -3.67 to 1.43 L; P = .39) and seventh (MD, -0.01 L; 95% CI, -0.45 to 0.42 L; P = .95) postoperative days. CONCLUSIONS: Balanced lower-chloride solutions significantly reduce the occurrence of DGF and provide an improved acid-base and electrolyte control in patients undergoing kidney transplantation.

Analysis of bupivacaine enantiomers in plasma as total and unbound concentrations using LC-MS/MS: Application in a pharmacokinetic study of a parturient with placental transfer.

Bupivacaine, a drug used in obstetric anesthesia and analgesia, is commercially available as a racemic mixture of the R-bupivacaine and S-bupivacaine enantiomers, which show differences in pharmacokinetics, efficacy and toxicity. Changes in bupivacaine plasma protein binding is of clinical relevance considering its high protein binding (approximately 95%) and its classification as an intermediate hepatic extraction ratio drug (E = 0.38). Furthermore, the plasma protein binding of bupivacaine is also of clinical relevance considering that pregnancy is a physiological condition associated with reduced plasma albumin concentration. Also, different pathological conditions, such as pre-eclampsia, can reduce the maternal plasma protein concentrations and consequently increase the bupivacaine placental transfer. This report describes the development and validation of analytical methods for the sequential analysis of the total and unbound concentrations of bupivacaine enantiomers in human plasma using liquid chromatography coupled to mass spectrometry (LC-MS/MS) with a sensitivity compatible with application in pharmacokinetic studies including placental transfer. Aliquots of 200 µL of plasma or plasma ultra-filtrate were extracted with n-hexane in alkaline medium after the deproteinization of the matrix with acetonitrile and water. The separation of bupivacaine enantiomers was obtained on a Chirex® 3020 chiral stationary phase column using as a mobile phase a mixture of 95% n-hexane:ethanol (80:20, v/v) at a flow rate of 0.8 mL/min. The lower limit of quantification was 0.25 ng of each enantiomer/mL of plasma as the total concentration and 0.125 ng of each enantiomer/mL of plasma as the unbound concentration. The methods were applied to study the pharmacokinetics of bupivacaine enantiomers after the administration of 2.5 mg of 0.5% racemic bupivacaine hydrochloride with 1:200,000 epinephrine via the epidural route to an HIV-positive parturient woman undergoing antiretroviral treatment. The parturient showed lower AUC0-∞ (25.42 vs. 30.57 ng.h/mL) and higher volume of distribution (841.96 vs 655.05 L) and total clearance (98.34 vs 81.79 L/h) for the R-bupivacaine enantiomer. The pharmacokinetics of bupivacaine were enantioselective displaying a lower plasma proportion of the enantiomer R-bupivacaine (AUC(R)/(S) ratio equal to 0.83). The placental transfer was approximately 60% for both bupivacaine enantiomers. The unbound fraction (Fu) for the R-bupivacaine enantiomer was higher (10.84%) than the eutomer S-bupivacaine (6.29%).

Time course of lead induced proteomic changes in gill of the Antarctic limpet Nacella Concinna (Gastropoda: Patellidae).

The effect of increasing levels of metals from anthropogenic sources on Antarctic invertebrates is poorly understood. Here we exposed limpets (Nacella concinna) to 0, 0.12 and 0.25 µg L− 1 lead for 12, 24, 48 and 168 h. We subsequently quantified the changes in protein abundance from gill, using 2D gel electrophoresis and mass spectrometry. We identified several antioxidant proteins, including the metal binding Mn-superoxide dismutase and ferritin, increasing abundances early on. Chaperones involved in the redox-dependent maturation of proteins in the endoplasmic reticulum (ER) showed higher abundance with lead at 48 h. Lead also increased the abundance of Zn-binding carbonic anhydrase at 12 h, suggesting a challenge to acid-base balance. Metabolic proteins increased abundance at 168 h, suggesting a greater ATP demand during prolonged exposure. Changes in abundance of the small G-protein cdc42, a signaling protein modifying cytoskeleton, increased early and subsequently reversed during prolonged exposure, possibly leading to the modification of thick filament structure and function. We hypothesize that the replacement of metals initially affected antioxidant proteins and increased the production of reactive oxygen species. This disrupted the redox-sensitive maturation of proteins in the ER and caused increased ATP demand later on, accompanied by changes in cytoskeleton. SIGNIFICANCE: Proteomic analysis of gill tissue in Antarctic limpets exposed to different concentrations of lead (Pb) over a 168 h time period showed that proteomic changes vary with time. These changes included an increase in the demand of scavenging reactive oxygen species, acid-base balance and a challenge to protein homeostasis in the endoplasmic reticulum early on and subsequently an increase in energy metabolism, cellular signaling, and cytoskeletal modifications. Based on this time course, we hypothesize that the main mode of action of lead is a replacement of metal-cofactors of key enzymes involved in the scavenging of reactive oxygen species and the regulation of acid-base balance.

The effect of NaCl 0.9% and NaCl 0.45% on sodium, chloride, and acid-base balance in a PICU population / Efeito do NaCl a 0,9% e do NaCl a 0,45% sobre o sódio, cloreto e equilíbrio ácido-base em uma população de UTIP

ABSTRACT OBJECTIVES: To study the effect of two intravenous maintenance fluids on plasma sodium (Na), and acid-base balance in pediatric intensive care patients during the first 24 h of hospitalization. METHODS: A prospective randomized controlled study was performed, which allocated 233 patients to groups: (A) NaCl 0.9% or (B) NaCl 0.45%. Patients were aged 1 day to 18 years, had normal electrolyte concentrations, and suffered an acute insult (medical/surgical). Main outcome measured: change in plasma sodium. Parametric tests: t-tests, ANOVA, X 2 statistical significance level was set at a = 0.05. RESULTS: Group A (n = 130): serum Na increased by 2.91 (±3.9) mmol/L at 24 h (p < 0.01); 2% patients had Na higher than 150 mmol/L. Mean urinary Na: 106.6 (±56.8) mmol/L. No change in pH at 0 and 24 h. Group B (n = 103): serum Na did not display statistically significant changes. Fifteen percent of the patients had Na < 135 mmol/L at 24 h. The two fluids had different effects on respiratory and post-operative situations. CONCLUSIONS: The use of saline 0.9% was associated with a lower incidence of electrolyte disturbances.

RESUMO OBJETIVO: Estudar o efeito de dois fluidos de manutenção intravenosos sobre o sódio (Na) plasmático e o equilíbrio ácido-base em pacientes de terapia intensiva pediátrica durante as primeiras 24 horas de internação. MÉTODOS: Foi feito um estudo controlado randomizado prospectivo. Alocamos aleatoriamente 233 pacientes para os grupos: (A) NaCl a 0,9% e (B) NaCl a 0,45%. Os pacientes com um dia a 18 anos apresentavam concentrações normais de eletrólitos e sofriam de insulto agudo (médico/cirúrgico). Principal resultado: variação no sódio plasmático. Testes paramétricos: teste t, Anova, qui-quadrado. O nível de relevância estatística foi estabelecido em a = 0,05. RESULTADOS: Grupo A (n = 130): o Na sérico aumentou 2,91 (± 3,9) mmol L-1 em 24 h (p < 0,01); 2% dos pacientes apresentaram Na acima de 150 mmol L-1. Concentração média de Na na urina: 106,6 (± 56,8) mmol L-1. Sem alteração no pH em 0 e 24 horas. Grupo B (n = 103): o Na sérico não apresentou alterações estatisticamente significativas; 15% dos pacientes apresentaram Na < 135 mmol L-1 em 24 h. Os dois fluidos tiveram efeitos diferentes sobre as situações respiratória e pós-operatória. CONCLUSÃO: O uso de solução fisiológica a 0,9% foi associado à menor incidência de distúrbios eletrolíticos.

Effects of goal-directed fluid therapy with different lactated Ringer's: hydroxyethyl starch ratios in hemorrhagic shock dogs.

The effects of goal-directed fluid therapy, with lactated Ringer's (LR) and 6% hydroxyethyl starch (HES) solution, on hemorrhagic shock dogs are unknown. We aimed to determine the optimal LR: HES ratio for the resuscitation of hemorrhagic shock dogs. Hemorrhagic shock was induced in 40 ventilated dogs by drawing an estimated 60% blood volume. The animals were randomly divided into five groups (N = 8) according to the LR: HES ratio of the resuscitation fluid (3:1, 2:1, 1:1, 1:2, and 1:3), and were then resuscitated for 24 h to reach the stroke volume variation (SVV) and hemoglobin (Hb) goals by fluid infusion and autologous blood perfusion. The extravascular lung water index (EVLWI), pH, partial pressure of oxygen (PaO2), base excess (BE), sodium, chloride, Hb and creatinine clearance (Clearcrea) were checked after 24 h (R24). The EVLWI of the 3:1 group at R24 were higher than that of the 1:3 group and the baseline value (P < 0.05), whereas the PaO2 was lower (P < 0.05). In contrast to the 3:1 group at R24 and baseline, plasma chloride and sodium in the 1:3 and 1:2 groups increased; however, pH, BE, and Clearcrea decreased (P < 0.05). No significant differences were found in the 1:1 and 2:1 groups at R24 compared with baseline (P > 0.05). Resuscitation with LR and HES at 2:1 and 1:1 ratios are superior in maintaining the acid-base, electrolyte, and lung water balances as well as renal function in hemorrhagic shock dogs than at ratios of 3:l, 1:2, and1:3.

The effect of NaCl 0.9% and NaCl 0.45% on sodium, chloride, and acid-base balance in a PICU population.

OBJECTIVES: To study the effect of two intravenous maintenance fluids on plasma sodium (Na), and acid-base balance in pediatric intensive care patients during the first 24h of hospitalization. METHODS: A prospective randomized controlled study was performed, which allocated 233 patients to groups: (A) NaCl 0.9% or (B) NaCl 0.45%. Patients were aged 1 day to 18 years, had normal electrolyte concentrations, and suffered an acute insult (medical/surgical). MAIN OUTCOME MEASURED: change in plasma sodium. Parametric tests: t-tests, ANOVA, X(2) statistical significance level was set at α=0.05. RESULTS: Group A (n=130): serum Na increased by 2.91 (±3.9)mmol/L at 24h (p<0.01); 2% patients had Na higher than 150 mmol/L. Mean urinary Na: 106.6 (±56.8)mmol/L. No change in pH at 0 and 24h. Group B (n=103): serum Na did not display statistically significant changes. Fifteen percent of the patients had Na<135 mmol/L at 24h. The two fluids had different effects on respiratory and post-operative situations. CONCLUSIONS: The use of saline 0.9% was associated with a lower incidence of electrolyte disturbances.

Blood gas analysis, anion gap, and strong ion difference in horses treated with polyethylene glycol balanced solution (PEG 3350) or enteral and parenteral electrolyte solutions / Hemogasometria, anion gap e diferença de íons fortes em equinos tratados com solução balanceada contendo polietilenoglicol (PEG 3350) ou soluções eletrolíticas enteral e parenteral

Large volumes of different electrolytes solutions are commonly used for ingesta hydration in horses with large colon impaction, but little is known about their consequences to blood acid-base balance. To evaluate the effects of PEG 3350 or enteral and parenteral electrolyte solutions on the blood gas analysis, anion gap and strong ion difference, five adult female horses were used in a 5x5 latin square design. The animals were divided in five groups and distributed to each of the following treatments: NaCl (0.9% sodium chloride solution); EES (enteral electrolyte solution), EES+LR (EES plus lactated Ringer's solution); PEG (balanced solution with PEG 3350) and PEG+LR (PEG plus lactated Ringer's solution). Treatments PEG or PEG + LR did not change or promoted minimal changes, while the EES caused a slight decrease in pH, but its association with lactated Ringer's solution induced increase in AG and SID values, as well as caused hypernatremia. In turn, the treatment NaCl generated metabolic acidosis. PEG 3350 did not alter the acid-base balance. Despite it's slight acidifying effect, the enteral electrolyte solution (EES) did not cause clinically relevant changes.(AU)

Grandes volumes de diferentes soluções eletrolíticas são comumente usados na hidratação da ingesta em equinos com compactação, mas pouco se sabe sobre suas consequências sobre o equilíbrio ácido base sanguíneo. Para avaliar os efeitos do PEG 3350 e soluções eletrolíticas enterais e parenterais sobre a hemogasometria, anion gap e diferença de íons fortes, foram utilizadas cinco fêmeas adultas em um quadrado latino 5x5. Os animais foram distribuídos em cinco grupos e submetidos a cada um dos seguintes tratamentos: solução NaCl (cloreto de sódio 0,9%); EES (solução eletrolítica enteral); EES + RL (solução eletrolítica enteral mais Ringer lactato); PEG 3350 (solução balanceada com PEG 3350) e PEG + RL (PEG 3350 mais Ringer lactato). Os tratamentos PEG ou PEG + RL não alteraram ou promoveram alterações mínimas, enquanto a EES ocasionou discreta diminuição no pH, mas sua associação com Ringer lactato induziu o aumento nos valores do AG e DIF, além de ocasionar hipernatremia. Por sua vez, o tratamento NaCl resultou em acidose metabólica hiperclorêmica. O PEG 3350 não alterou o equilíbrio ácido base. Apesar do seu discreto efeito acidificante, a solução eletrolítica enteral (EES) não promoveu alteração clínica relevante.(AU)

Systemic and microcirculatory effects of dobutamine in patients with septic shock.

PURPOSE: The aim of this study was to characterize the cardiovascular responses to dobutamine and their predictors. Our hypotheses were that dobutamine mainly produces tachycardia and vasodilation and fails to improve the microcirculation of patients with septic shock. MATERIALS AND METHODS: Systemic hemodynamics and sublingual microcirculation were evaluated with dobutamine (0, 2.5, 5.0, and 10.0 µg kg(-1) min(-1)) in 23 patients with septic shock. RESULTS: Dobutamine increased heart rate, cardiac index, and stroke volume index (SVI). Mean blood pressure was unchanged, and systemic vascular resistance decreased. Individual responses were heterogeneous. Stroke volume index increased in 52% of the patients. These patients showed lower changes in mean blood pressure (3 ± 16 mm Hg vs -10 ± 6 mm Hg, P < .05) and higher increases in cardiac index (1.47 ± 0.93 L m(-1) m(-2) vs 0.20 ± 0.5 L m(-1) m(-2)) than did nonresponders. Changes in SVI significantly correlated with echocardiographic left ventricular ejection fraction (r = 0.55). In the whole group, perfused capillary density remained unchanged (14.0 ± 4.3 mm/mm(2) vs 14.8 ± 3.7 mm/mm(2)), but improved if basal values were 12 mm/mm(2) or less (9.1 ± 4.3 mm/mm(2) vs 12.5 ± 4.8 mm/mm(2)). CONCLUSIONS: Dobutamine produced variable hemodynamic effects. Systolic dysfunction was the only variable associated with increases in SVI. Finally, dobutamine only improved sublingual microcirculation when severe alterations were found at baseline.

Transcriptomic profiles of Japanese medaka (Oryzias latipes) in response to alkalinity stress.

Oryzias latipes (Adrianichthyidae), known as Japanese medaka or Japanese killifish, is a small 2-4 cm long fish common in rice paddies in coastal Southeast Asia and is also a popular aquarium fish. It has been widely used as a research model because of its small size and because it is very easy to rear. Alkalinity stress is considered to be one of the major stressors on fish in saline-alkaline water. As very little is known about molecular genetic responses of aquatic organisms to alkalinity stress, we examined genome-wide gene expression profiles of Japanese medaka in response to carbonate alkalinity stress. Adult fish were exposed to freshwater and high carbonate alkaline water in the laboratory. We designed a microarray containing 26,429 genes for measuring gene expression change in the gills of the fish exposed to high carbonate alkalinity stress. Among these genes, 512 were up-regulated and 501 were down-regulated in the gills. These differentially expressed genes can be divided into gene groups using gene ontology, including biological processes, cellular components and molecular function. These gene groups are related to acid-base and ion regulation, cellular stress response, metabolism, immune response, and reproduction processes. Biological pathways including amino sugar and nucleotide sugar metabolism, porphyrin and chlorophyll metabolism, metabolism of xenobiotics by cytochrome P450, drug metabolism, aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, ascorbate and aldarate metabolism, pentose and glucuronate interconversions, glutathione metabolism, and fructose and mannose metabolism were significantly up-regulated. Alkalinity stress stimulates the energy and ion regulation pathways, and it also slows down the pathways related to the immune system and reproduction.

Cardiopulmonary and analgesic effects of caudal epidurally administered ropivacaine in cattle.

OBJECTIVE: To assess cardiopulmonary and analgesic effects after administration of ropivacaine into the caudal epidural space of cattle. STUDY DESIGN: Prospective, single-dose trial. ANIMALS: Eight healthy mixed breed cows aged 8 ± 5 years and weighing 507 ± 112 kg. METHODS: Caudal epidural anesthesia was produced in cows with 0.75% ropivacaine (0.11 mg kg(-1)). Onset time, duration and cranial spread of analgesia were recorded. Heart rate (HR), respiratory rate (f(R)), rectal temperature (RT), and mean arterial blood pressure (MAP) were measured prior to epidural administration (T(0) ) and at 15, 30, 60, 120, 180 and 240 minutes after epidural administration (T(15), T(30), T(60) , T(120) , T(180) and T(240) ). Arterial blood acid-base balance (pH, standard bicarbonate and base excess), gas tension (PaO(2), PaCO(2), SaO(2)) and electrolytes (Na(+), K(+), iCa(2+),Cl(-)) were recorded at T(0), T(30), T(60), T(120), T(180) and T(240). Ataxia was evaluated at T(0), T(30), T(60), T(120), T(180) and T(240) and at 1 hour intervals thereafter until analgesia was no longer present in each animal. RESULTS: Epidurally administered ropivacaine induced variable analgesia extending bilaterally from the coccyx to S3. Time to onset of analgesia and mean duration in the perineal area were 15 ± 4 and 359 ± 90 minutes, respectively. Respiratory rate and RT increased from T(120) to T(240) when compared to the value at T(0) . Ionized calcium and chloride concentrations increased at T(180) and T(240) when compared to T(0). The other variables were not significantly different from baseline values (p > 0.05). Four animals were mildly ataxic. CONCLUSION AND CLINICAL RELEVANCE: Ropivacaine (0.75%, 0.11 mg kg(-1)) can be administered by caudal epidural injection to produce prolonged bilateral perineal analgesia with minimal ataxia and cardiopulmonary changes in standing cattle.

Vetrabutine clorhydrate use in dystocic farrowings minimizes hemodynamic sequels in piglets.

The objective was to measure the effects of VC (a uterotonic drug with vasodilator effects) in eutocic and dystocic sows, on the acid-base balance and some vitality traits of piglets at birth. Farrowing was induced with prostaglandin F2α. Four groups of sows (20 sows/group) were monitored; Groups 1 and 2 were eutocic sows, whereas Groups 3 and 4 were dam-fetal dystocic sows. Groups 1 and 3 (control) were given saline, whereas Groups 2 and 4 were given VC im (1.66 mg/kg of body weight) after the first piglet was born. Piglets' physio-metabolic performance was monitored peripartum. Treatment with VC reduced (P<0.0001) the percentage of intrapartum stillbirths in sows either with eutocic (5.2 vs. 10.0%) and dystocic (7.6 vs. 16.7%) farrowings and increased (P<0.0001) the number of pigs born alive without any evidence of AFS (89.9 vs. 79.9%, eutocic and 81.6 vs. 65.2%, dystocic). In addition, for the group of pigs with no acute fetal suffering (AFS), VC treatment enhanced survival responses with a half point grater vitality score in Group 4; it also reduced the latency to first teat contact by 6 min (P<0.05) in both treated groups compared to controls; and it improved the condition of the pigs' umbilical cord, with more adhered (98 vs. 86% in eutocic and 88 vs. 80% in dystocic; P<0.05) and less ruptured cords. Moreover, VC reduced the severity of adverse physio-metabolic indicators and the acid-base balance of piglets with AFS at birth by lowering blood lactate (89.8 vs. 93.5 mmol/L in eutocic groups and 94.6 vs. 100.2 mmol/L in dystocic groups; P<0.05), PaCO2 and Ca2+, and by increasing blood pH, HCO3 and PaO2 levels (P<0.05).

Action of ANP on the nongenomic dose-dependent biphasic effect of aldosterone on NHE1 in proximal S3 segment.

The rapid (2 min) nongenomic effects of aldosterone (ALDO) and/or spironolactone (MR antagonist), RU 486 (GR antagonist), atrial natriuretic peptide (ANP) and dimethyl-BAPTA (BAPTA) on the intracellular pH recovery rate (pHirr) via NHE1 (basolateral Na⁺/H⁺ exchanger isoform), after the acid load induced by NH4Cl, and on the cytosolic free calcium concentration ([Ca²âº](i)) were investigated in the proximal S3 segment isolated from rats, by the probes BCECF-AM and FLUO-4-AM, respectively. The basal pHi was 7.15±0.008 and the basal pHirr was 0.195±0.012 pH units/min (number of tubules/number of tubular areas=16/96). Our results confirmed the rapid biphasic effect of ALDO on NHE1: ALDO (10⁻¹² M) increases the pHirr to approximately 59% of control value, and ALDO (10⁻6 M) decreases it to approximately 49%. Spironolactone did not change these effects, but RU 486 inhibited the stimulatory effect and maintained the inhibitory effect. ANP (10⁻6 M) or BAPTA (5×10⁻5 M) alone had no significant effect on NHE1 but prevented both effects of ALDO on this exchanger. The basal [Ca²âº](i) was 104±3 nM (15), and ALDO (10⁻¹² or 10⁻6 M) increased the basal [Ca²âº](i) to approximately 50% or 124%, respectively. RU 486, ANP and BAPTA decreased the [Ca²âº](i) and inhibited the stimulatory effect of both doses of ALDO. The results suggest the involvement of GR on the nongenomic effects of ALDO and indicate a pHirr-regulating role for [Ca²âº](i) that is mediated by NHE1, stimulated/impaired by ALDO, and affected by ANP or BAPTA with ALDO. The observed nongenomic hormonal interaction in the S3 segment may represent a rapid and physiologically relevant regulatory mechanism in the intact animal under conditions of volume alterations.

Acid-base and biochemical stabilization and quality of recovery in male cats with urethral obstruction and anesthetized with propofol or a combination of ketamine and diazepam.

This study compared acid-base and biochemical changes and quality of recovery in male cats with experimentally induced urethral obstruction and anesthetized with either propofol or a combination of ketamine and diazepam for urethral catheterization. Ten male cats with urethral obstruction were enrolled for urethral catheterization and anesthetized with either ketamine-diazepam (KD) or propofol (P). Lactated Ringer's solution was administered by intravenous (IV) beginning 15 min before and continuing for 48 h after relief of urethral obstruction. Quality of recovery and time to standing were evaluated. The urethral catheter was maintained to measure urinary output. Hematocrit (Hct), total plasma protein (TPP), albumin, total protein (TP), blood urea nitrogen (BUN), creatinine, pH, bicarbonate (HCO3-), chloride, base excess, anion gap, sodium, potassium, and partial pressure of carbon dioxide in mixed venous blood (pvCO2) were measured before urethral obstruction, at start of fluid therapy (0 h), and at subsequent intervals. The quality of recovery and time to standing were respectively 4 and 75 min in the KD group and 5 and 16 min in the P group. The blood urea nitrogen values were increased at 0, 2, and 8 h in both groups. Serum creatinine increased at 0 and 2 h in cats administered KD and at 0, 2, and 8 h in cats receiving P, although the values were above the reference range in both groups until 8 h. Acidosis occurred for up to 2 h in both groups. Acid-base and biochemical stabilization were similar in cats anesthetized with propofol or with ketamine-diazepam. Cats that received propofol recovered much faster, but the ketamine-diazepam combination was shown to be more advantageous when treating uncooperative cats as it can be administered by intramuscular (IM) injection.

Impact of Plasma-Lyte pH 7.4 on acid-base status and hemodynamics in a model of controlled hemorrhagic shock.

OBJECTIVE: Intravenous infusion of crystalloid solutions is a cornerstone of the treatment of hemorrhagic shock. However, crystalloid solutions can have variable metabolic acid-base effects, perpetuating or even aggravating shock-induced metabolic acidosis. The aim of this study was to compare, in a controlled volume-driven porcine model of hemorrhagic shock, the effects of three different crystalloid solutions on the hemodynamics and acid-base balance. METHODS: Controlled hemorrhagic shock (40% of the total blood volume was removed) was induced in 18 animals, which were then treated with normal saline (0.9% NaCl), Lactated Ringer's Solution or Plasma-Lyte pH 7.4, in a blinded fashion (n = 6 for each group). Using a predefined protocol, the animals received three times the volume of blood removed. RESULTS: The three different crystalloid infusions were equally capable of reversing the hemorrhage-induced low cardiac output and anuria. The Lactated Ringer's Solution and Plasma-Lyte pH 7.4 infusions resulted in an increased standard base excess and a decreased serum chloride level, whereas treatment with normal saline resulted in a decreased standard base excess and an increased serum chloride level. The Plasma-Lyte pH 7.4 infusions did not change the level of the unmeasured anions. CONCLUSION: Although the three tested crystalloid solutions were equally able to attenuate the hemodynamic and tissue perfusion disturbances, only the normal saline induced hyperchloremia and metabolic acidosis.

The effects of 6% hydroxyethyl starch-hypertonic saline in resuscitation of dogs with hemorrhagic shock.

BACKGROUND: Hemodynamic and global oxygen transport variables have failed to reflect splanchnic hypoperfusion, resulting in a failure to recognize inadequately treated hemorrhagic shock. Volemic expansion after fluid resuscitation is essential to improve global and regional oxygen in hemorrhagic shock. We hypothesized that, in contrast to conventional plasma expanders, the smaller volemic expansion from 7.5 NaCl/6% hydroxyethyl starch (HHES) solution administration in hemorrhagic shock may provide lesser systemic oxygen delivery and gastric perfusion. We used hemorrhaged dogs to compare intravascular volume expansion and the early systemic oxygenation and gastric perfusion effects of fixed fluid bolus administration, which are usually used in clinical situations with severe hemorrhage, of HHES, lactated Ringer (LR), and 6% hydroxyethyl starch (HES) solutions. METHODS: Thirty dogs were bled (30 mL · kg(-1)) to hold mean arterial blood pressure at 40 to 50 mm Hg over 45 minutes and were resuscitated in 3 groups: LR (n = 10) at 3:1 ratio to shed blood; HES (mean molecular weight 130 kDa, degree of substitution 0.4) (n = 10) at 1:1 to shed blood; and HHES (n = 10), 4 mL · kg(-1). Intravascular volume expansion (Evans blue and hemoglobin dilution), hemodynamic, systemic oxygenation, venous-to-arterial CO(2) gradient (Pv-aCO(2)), and gastric intramucosal-arterial PCO(2) gradient (PCO(2) gap) variables were measured at baseline, after 45 minutes of hemorrhage, and 5, 45, and 90 minutes after fluid resuscitation. RESULTS: HHES increased blood volume because of the high volume expansion efficiency, but intravascular volume expansion with this solution was the smallest of the solutions (P < 0.05). All 3 solutions induced a similar hemodynamic performance but HHES showed lower mixed venous PO(2) and higher systemic oxygenation extraction, Pv-aCO(2), and PCO(2) gap than LR and HES (P < 0.05). CONCLUSIONS: In dogs submitted to pressure-guided hemorrhagic shock and fixed-volume resuscitation, the smaller intravascular volume expansion from HHES solutions provides worse recovery of systemic oxygenation and gastric perfusion compared with LR and HES solutions despite its high volume expansion efficiency, which was limited by low infused volume.

Impact of Plasma-Lyte pH 7.4 on acid-base status and hemodynamics in a model of controlled hemorrhagic shock

OBJECTIVE: Intravenous infusion of crystalloid solutions is a cornerstone of the treatment of hemorrhagic shock. However, crystalloid solutions can have variable metabolic acid-base effects, perpetuating or even aggravating shock-induced metabolic acidosis. The aim of this study was to compare, in a controlled volume-driven porcine model of hemorrhagic shock, the effects of three different crystalloid solutions on the hemodynamics and acid-base balance. METHODS: Controlled hemorrhagic shock (40 percent of the total blood volume was removed) was induced in 18 animals, which were then treated with normal saline (0.9 percent NaCl), Lactated Ringer's Solution or Plasma-Lyte pH 7.4, in a blinded fashion (n = 6 for each group). Using a predefined protocol, the animals received three times the volume of blood removed. RESULTS: The three different crystalloid infusions were equally capable of reversing the hemorrhage-induced low cardiac output and anuria. The Lactated Ringer's Solution and Plasma-Lyte pH 7.4 infusions resulted in an increased standard base excess and a decreased serum chloride level, whereas treatment with normal saline resulted in a decreased standard base excess and an increased serum chloride level. The Plasma-Lyte pH 7.4 infusions did not change the level of the unmeasured anions. CONCLUSION: Although the three tested crystalloid solutions were equally able to attenuate the hemodynamic and tissue perfusion disturbances, only the normal saline induced hyperchloremia and metabolic acidosis.

Effect of chloride dialysate concentration on metabolic acidosis in aintenance hemodialysis patients

Hyperchloremia is one of the multiple etiologies of metabolic acidosis in hemodialysis (HD) patients. The aim of the present study was to determine the influence of chloride dialysate on metabolic acidosis control in this population. We enrolled 30 patients in maintenance HD program with a standard base excess (SBE) ≤2 mEq/L and urine output of less than 100 mL/24 h. The patients underwent dialysis three times per week with a chloride dialysate concentration of 111 mEq/L for 4 weeks, and thereafter with a chloride dialysate concentration of 107 mEq/L for the next 4 weeks. Arterial blood was drawn immediately before the second dialysis session of the week at the end of each phase, and the Stewart physicochemical approach was applied. The strong ion gap (SIG) decreased (from 7.5 ± 2.0 to 6.2 ± 1.9 mEq/L, P = 0.006) and the standard base excess (SBE) increased after the use of 107 mEq/L chloride dialysate (from -6.64 ± 1.7 to -4.73 ± 1.9 mEq/L, P < 0.0001). ∆SBE was inversely correlated with ∆SIG during the phases of the study (Pearson r = -0.684, P < 0.0001) and there was no correlation with ∆chloride. When we applied the Stewart model, we demonstrated that the lower concentration of chloride dialysate interfered with the control of metabolic acidosis in HD patients, surprisingly, through the effect on unmeasured anions.

Effect of chloride dialysate concentration on metabolic acidosis in maintenance hemodialysis patients.

Hyperchloremia is one of the multiple etiologies of metabolic acidosis in hemodialysis (HD) patients. The aim of the present study was to determine the influence of chloride dialysate on metabolic acidosis control in this population. We enrolled 30 patients in maintenance HD program with a standard base excess (SBE) ≤2 mEq/L and urine output of less than 100 mL/24 h. The patients underwent dialysis three times per week with a chloride dialysate concentration of 111 mEq/L for 4 weeks, and thereafter with a chloride dialysate concentration of 107 mEq/L for the next 4 weeks. Arterial blood was drawn immediately before the second dialysis session of the week at the end of each phase, and the Stewart physicochemical approach was applied. The strong ion gap (SIG) decreased (from 7.5 ± 2.0 to 6.2 ± 1.9 mEq/L, P = 0.006) and the standard base excess (SBE) increased after the use of 107 mEq/L chloride dialysate (from -6.64 ± 1.7 to -4.73 ± 1.9 mEq/L, P < 0.0001). ∆SBE was inversely correlated with ∆SIG during the phases of the study (Pearson r = -0.684, P < 0.0001) and there was no correlation with ∆chloride. When we applied the Stewart model, we demonstrated that the lower concentration of chloride dialysate interfered with the control of metabolic acidosis in HD patients, surprisingly, through the effect on unmeasured anions.

Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study.

INTRODUCTION: Our goal was to assess the effects of titration of a norepinephrine infusion to increasing levels of mean arterial pressure (MAP) on sublingual microcirculation. METHODS: Twenty septic shock patients were prospectively studied in two teaching intensive care units. The patients were mechanically ventilated and required norepinephrine to maintain a mean arterial pressure (MAP) of 65 mmHg. We measured systemic hemodynamics, oxygen transport and consumption (DO2 and VO2), lactate, albumin-corrected anion gap, and gastric intramucosal-arterial PCO2 difference (DeltaPCO2). Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. After basal measurements at a MAP of 65 mmHg, norepinephrine was titrated to reach a MAP of 75 mmHg, and then to 85 mmHg. Data were analyzed using repeated measurements ANOVA and Dunnett test. Linear trends between the different variables and increasing levels of MAP were calculated. RESULTS: Increasing doses of norepinephrine reached the target values of MAP. The cardiac index, pulmonary pressures, systemic vascular resistance, and left and right ventricular stroke work indexes increased as norepinephrine infusion was augmented. Heart rate, DO2 and VO2, lactate, albumin-corrected anion gap, and DeltaPCO2 remained unchanged. There were no changes in sublingual capillary microvascular flow index (2.1 +/- 0.7, 2.2 +/- 0.7, 2.0 +/- 0.8) and the percent of perfused capillaries (72 +/- 26, 71 +/- 27, 67 +/- 32%) for MAP values of 65, 75, and 85 mmHg, respectively. There was, however, a trend to decreased capillary perfused density (18 +/- 10,17 +/- 10,14 +/- 2 vessels/mm2, respectively, ANOVA P = 0.09, linear trend P = 0.045). In addition, the changes of perfused capillary density at increasing MAP were inversely correlated with the basal perfused capillary density (R2 = 0.95, P < 0.0001). CONCLUSIONS: Patients with septic shock showed severe sublingual microcirculatory alterations that failed to improve with the increases in MAP with norepinephrine. Nevertheless, there was a considerable interindividual variation. Our results suggest that the increase in MAP above 65 mmHg is not an adequate approach to improve microcirculatory perfusion and might be harmful in some patients.

NHE1, NHE2, and NHE4 contribute to regulation of cell pH in T84 colon cancer cells.

The isoforms of the Na+/H+ exchanger present in T84 human colon cells were identified by functional and molecular methods. Cell pH was measured by fluorescence microscopy using the probe BCECF. Based on the pH recovery after an ammonium pulse and determination of buffering capacity of these cells, the rate of H+ extrusion (JH) was 3.68 mM/min. After the use of the amiloride derivative HOE-694 at 25 microM, which inhibits the isoforms NHE1 and NHE2, there remained 43% of the above transport rate, the nature of which was investigated. Evidence of the presence of NHE1, NHE2, and NHE4 was obtained by reverse transcriptase polymerase chain reaction (RT-PCR) (mRNA) and Western blot. There was no decrease of JH by the NHE3 inhibitor S3226 (1 microM) and no evidence of this isoform by RT-PCR was found. The following functional evidence for the presence of NHE4 was obtained: 25 microM EIPA abolished JH entirely, but NHE4 was not inhibited at 10 microM; substitution of Na by K increased the remainder, a property of NHE4; hypertonicity also increased this fraction of JH. Cl--dependent NHE was not detected: in 0 Cl- solutions JH was increased and not reduced. In 0 Cl- cell volume decreased significantly, which was abolished by the Cl- channel blocker NPPB, indicating that the 0 Cl- effect was because of reduction of cell volume. In conclusion, T84 human colon cells contain three isoforms of the Na+/H+ exchanger, NHE1, NHE2, and NHE4, but not the Cl-dependent NHE.