Intraoperative Oxygen Consumption During Liver Transplantation.

BACKGROUND: The aim of this study was to investigate the changes in oxygen consumption during liver transplantation and to examine the relationship between intraoperatively elevated systemic oxygen consumption and postoperative liver function. METHODS: This study was performed in 33 adult patients undergoing liver transplantation between September 2011 and March 2014. We measured intraoperative oxygen consumption through the use of indirect calorimetry, preoperative and intraoperative data, liver function tests, and postoperative complications and outcomes. RESULTS: The mean age of patients was 52 ± 9.7 years; 14 (42%) of them were women. Average Model for End-Stage Liver Disease scores were 20 ± 8.9. Oxygen consumption significantly increased after reperfusion from 172 ± 30 mL/min during the anhepatic phase to 209 ± 30 mL/min (P < .0001). We divided patients into 2 groups according to the increase in oxygen consumption after reperfusion (oxygen consumption after reperfusion minus anhepatic phase oxygen consumption: 40 mL/min increase as cutoff). The higher consumption group had a longer cold ischemia time and higher postoperative aspartate aminotransferase and alanine aminotransferase levels as compared with the lower oxygen consumption group. There were no statistically significant differences in major postoperative complications, but the higher oxygen consumption group tended to have shorter hospital stays than the lower consumption group (58 versus 95 days). CONCLUSIONS: We have demonstrated that oxygen consumption significantly increased after reperfusion. Furthermore, this increased oxygen consumption was associated with a longer cold ischemia time and shorter hospital stays.

Two cases of variceal haemorrhage during living-donor liver transplantation.

Some patients with cirrhosis experience rupture of venous varices before operation, and liver transplantation is a therapy of last resort for these patients. However, we have experienced two cases of intraoperative rupture in whom no abnormalities of the venous varices were seen on endoscopy before operation. One patient with ruptured gastrointestinal varices was treated by direct surgical ligation and the other with ruptured oesophageal gastric varices, spontaneously recovered with a Sengstaken-Blakemore tube. These cases suggest that acute variceal haemorrhage should always be considered as a possibility during living-donor liver transplantation in patients with a history of upper gastrointestinal bleeding. Careful observation of the nasogastic tube is important during clamping of the hepatic portal vein.

Hemin treatment abrogates monocrotaline-induced pulmonary hypertension.

Treatment of rats with monocrotaline (MCT), a pyrrolizidine alkaloid plant toxin, is known to cause pulmonary hypertension (PH), and it has been used as a useful experimental model of PH. Recent findings suggested that pulmonary inflammation may play a significant role in the pathogenesis of MCT-induced PH. We also demonstrated that, following MCT administration to rats, there was a significant and sustained increase in the pulmonary expression of heme oxygenase-1 (HO-1), which is known to be induced by various oxidative stresses, including inflammation and free heme, and is thought to be essential in the protection against oxidative tissue injuries. In this study, we administered hemin (ferriprotoporphyrin chloride, 30 micromol/kg b.w., subcutaneously), a potent inducer of HO-1, every 3 days to rats following subcutaneous administration of MCT (60 mg/kg) and examined its effect on MCT-induced PH and pulmonary inflammation. MCT administration caused pulmonary arterial wall thickening with marked elevation of right ventricular pressure, in association with prominent pulmonary inflammation as revealed by the increase in gene expression of tumor necrosis factor-alpha and the number of infiltrated neutrophils in the lung. In contrast, hemin treatment of MCT-administered animals, which led to a further increase in pulmonary HO-1 mRNA expression, significantly ameliorated MCT-induced PH as well as tissue inflammation. These findings suggest that hemin treatment ameliorates MCT-induced PH possibly mediated through induction of pulmonary HO-1 which leads to the attenuation of pulmonary inflammation.

Acid-base balance in combined severe hepatic and renal failure: a quantitative analysis.

BACKGROUND: Severe hepatic failure (SHF) commonly leads to major changes in acidbase balance status. However, the direct effects of liver failure per se on acid base balance are poorly understood because this condition is usually associated with acute renal failure (ARF). AIM: To assess the effect of SHF on acid-base balance. DESIGN: Retrospective laboratory investigation. SUBJECTS: Thirty-seven critically ill patients with SHF complicated by ARF, and 42 patients with severe ARF without liver failure prior to renal replacement therapy. INTERVENTION: Retrieval of clinical and laboratory data from prospective unit and laboratory databases. METHODS: Quantitative acid-base assessment using Stewart-Figge methodology. Comparison of findings between the two groups. Comparison of demographic and clinical features. RESULTS: Patients with combined SHF and ARF were younger and had significantly higher mean bilirubin, ALT and INR levels (p<0.0001). Their mean lactate concentration was higher (6.4 vs. 2.1 mmol/L; p<0.0001) leading to a greater anion gap (25.8 vs. 16.1 mmol/L; p<0.0001). The ionized calcium concentration (1.00 vs. 1.15 mmol/L; p<0.0001) was lower but the strong ion difference apparent (SIDa) was greater (42.0 vs. 38.0 mEq/L; p<0.005) due to hypochloremia. The albumin concentration was low but higher than in control patients (28 vs. 24 g/L; p<0.01) and the calculated strong ion gap (SIG) was greater (12.6 vs. 9.3 mEq/L; p<0.01). The base excess was similar to controls and the pH was preserved in the near normal range by marked hypocapnea. CONCLUSIONS: Combined SHF and ARF is a syndrome with unique acid-base changes due mostly to lactic metabolic acidosis and, in smaller part, to the accumulation of unmeasured anions. This acidosis, like that of ARF, is attenuated by hypoalbuminemia, by a unique preservation of the SIDa due to hypochloremia, and by marked hypocapnea.

Hyperglycemia and the outcome of pediatric cardiac surgery patients requiring peritoneal dialysis.

OBJECTIVE: To study the nature of the association between glycemia and ICU mortality in pediatric cardiac surgery patients treated with peritoneal dialysis (PD). MATERIALS AND METHODS: Retrospective observational study in the ICU of a tertiary hospital involving forty pediatric cardiac surgery patients treated with PD. We selected patients requiring PD, extracted glucose measurements and nutritional intake data during ICU stay and calculated mean and maximum blood glucose values i) during ICU stay; ii) during dependence on PD; and iii) during independence from PD. We statistically assessed the relationship between glycemia-related variables and ICU mortality. MEASUREMENTS AND RESULTS: Twenty-two patients treated with PD died (mortality 55%). In the PD cohort, 9725 blood glucose measurements were performed (every 3.3 hours on average). The mean glycemia during dependence on PD was significantly higher in non-survivors than survivors (p<0.0001), but not during independence from PD (p=0.49). The area under the receiver operator characteristic curve for the mean glycemia during dependence on PD was significantly greater than that obtained during independence from PD. Even after adjustment for severity of illness using multivariate logistic analysis, the mean glycemia and calorie intake during PD were significant and independent predictors of ICU mortality. CONCLUSIONS: A higher mean blood glucose concentration during PD, but not during PD-free periods was associated with greater ICU mortality. Mean glycemia and calorie intake during PD were significant and independent predictors of ICU mortality.

Heme oxygenase-1: a fundamental guardian against oxidative tissue injuries in acute inflammation.

Free heme contributes as a major threat to the oxidative tissue injuries because it catalyzes the formation of reactive oxygen species. When free heme concentration is increased, it results in the induction of heme oxygenase-1 (HO-1), which then breaks free heme down. As such, HO-1 plays a pivotal role in the protection of tissues from oxidative injuries.

Patient and kidney survival by dialysis modality in critically ill patients with acute kidney injury.

Using a large, international cohort, we sought to determine the effect of initial technique of renal replacement therapy (RRT) on the outcome of acute renal failure (ARF) in the intensive care unit (ICU). We enrolled 1218 patients treated with continuous RRT (CRRT) or intermittent RRT (IRRT) for ARF in 54 ICUs in 23 countries. We obtained demographic, biochemical and clinical data and followed patients to either death or hospital discharge. Information was analyzed to assess the independent impact of treatment choice on survival and renal recovery. Patients treated first with CRRT (N=1006, 82.6%) required vasopressor drugs and mechanical ventilation more frequently compared to those receiving IRRT (N=212, 17.4%), (p<0.0001). Unadjusted hospital survival was lower (35.8% vs. 51.9%, p<0.0001). However, unadjusted dialysis-independence at hospital discharge was higher after CRRT (85.5% vs. 66.2%, p<0.0001). Multivariable logistic regression showed that choice of CRRT was not an independent predictor of hospital survival or dialysis-free hospital survival. However, the choice of CRRT was a predictor of dialysis independence at hospital discharge among survivors (OR: 3.333, 95% CI: 1.845 - 6.024, p<0.0001). Further adjustment using a propensity score did not significantly change these results. We conclude that worldwide, the choice of CRRT as initial therapy is not a predictor of hospital survival or dialysis-free hospital survival but is an independent predictor of renal recovery among survivors.

Heme arginate pretreatment attenuates pulmonary NF-kappaB and AP-1 activation induced by hemorrhagic shock via heme oxygenase-1 induction.

Hemorrhagic shock followed by resuscitation (HSR) induces oxidative stress that leads to acute lung injury. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, is induced by oxidative stress and is thought to play an important role in the protection from oxidative tissue injuries. We previously demonstrated that HO-1 induction by heme arginate (HA), a strong inducer of HO-1, ameliorated HSR-induced lung injury and inflammation. Cellular redox state is known to modulate the DNA biding activity of the transcription factors; nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). In the present study, we treated rats with HA (30 mg/kg of hemin) 18 h prior to HSR and examined its effect on the DNA binding activity of NF-kappaB and AP-1 at 1.5 h after HSR. HSR significantly increased the DNA binding activity of NF-kappaB as well as AP-1, while HA pretreatment markedly attenuated the activities of these transcription factors. In contrast, administration of tin mesoporphyrin, a specific competitive inhibitor of HO activity, to HA-pretreated animals abolished the suppressive effect of HA on the activities of NF-kappaB and AP-1, and increased these activities to almost the same level as those in HSR animals. Our findings indicate that HA pretreatment can significantly suppress the increased activity of NF-kappaB and AP-1 induced by HSR by virtue of its ability to induce HO-1. Our findings also suggest that HO-1 induced by HA pretreatment ameliorates HSR-induced lung injury at least in part mediated through the suppression of the activities of these transcription factors.

Effect of low-dose vasopressin infusion on vital organ blood flow in the conscious normal and septic sheep.

The effect of low-dose vasopressin (AVP) on vital regional circulations may be clinically relevant but has not been fully described. We sought to determine the effect of low-dose AVP on systemic haemodynamics, coronary, mesenteric and renal circulations in the conscious normal and septic mammal. We studied seven Merino sheep using a prospective randomized cross-over double-blind placebo-controlled animal design. We inserted flow probes around aorta, coronary, mesenteric and renal arteries and, three weeks later, we infused low-dose AVP (0.02 IU/min) or placebo in the normal and septic state induced by intravenous E. coli. In normal sheep, AVP (0.02 IU/min) induced a 17% decrease in mesenteric blood flow (393.0+/-134.9 vs 472.1+/-163.8 ml/min, P<0.05) and a 14% decrease in mesenteric conductance (P<0.05). In septic sheep, AVP decreased heart rate and cardiac output by 28% and 22%, respectively (P<0.05). It also decreased mesenteric blood flow and mesenteric conductance by 23% (flow: 468.5+/-159.7 vs 611.3+/-136.3 ml/min, P<0.05; conductance: 6.3+/-2.7 vs 8.2+/-2.7 ml/min/mmHg; P<0.05). Renal blood flow was unchanged but urine output and creatinine clearance increased (P<0.05). We conclude that low-dose AVP infusion has similar effects in the normal and septic mammalian circulation: bradycardia, decreased cardiac output, decreased mesenteric blood flow and conductance and increased urine output and creatinine clearance. This information is important to clinicians considering its administration in humans.

Acid-base balance during continuous veno-venous hemofiltration: the impact of severe hepatic failure.

BACKGROUND: Continuous renal replacement therapy (CRRT) affects acid-base balance but the influence of severe hepatic failure (SHF) on this effect is unknown. AIM: To assess the effect of SHF on acid-base balance in patients receiving CVVH. DESIGN: Retrospective laboratory investigation. SUBJECTS: Forty patients with SHF and acute renal failure (ARF) treated with CVVH and 42 critically ill patients with severe ARF but no liver disease also treated with CVVH (controls). INTERVENTION: Retrieval of clinical and laboratory data from prospective unit and laboratory databases. METHODS: Quantitative acid-base status assessment using the Stewart-Figge methodology. Comparison of findings between the two groups. RESULTS: Although CVVH had a major effect on acid base balance in both groups, patients with SHF had a higher mean lactate concentrations (4.8 vs. 3.1 mmol/L; p<0.0005), a greater base deficit compared to controls (-1 vs. 4.1 mEq/L; p<0.0001) and a lower PaCO 2 tension (36.8 vs. 42.5 mmHg; p<0.0001), despite the use of bicarbonate replacement fluid. The acidifying effect of hyperlactatemia was slightly worsened by an increased strong ion gap (9.3 vs. 4.9 mEq/L; p<0.0001). It was, however, attenuated by an increased strong ion difference apparent (SIDa) (43.6 vs. 41.9 mEq/L; p<0.05) secondary to hypochloremia (96 vs. 100 mmol/L; p<0.0001) and by hypoalbuminemia, although hypoalbuminemia in SHF patients (26 vs. 23; p<0.005) was less pronounced than in controls. CONCLUSION: The use of CVVH does not fully correct the independent acidifying effect of liver failure on acid-base status. Increased lactate and strong ion gap values maintain a persistent base deficit despite the alkalinizing effects of hypoalbuminemia and hypochloremia. The correction of acidosis in SHF patients may require more intensive CVVH.

Strong ions, weak acids and base excess: a simplified Fencl-Stewart approach to clinical acid-base disorders.

BACKGROUND: The Fencl-Stewart approach to acid-base disorders uses five equations of varying complexity to estimate the base excess effects of the important components: the strong ion difference (sodium and chloride), the total weak acid concentration (albumin) and unmeasured ions. Although this approach is straightforward, most people would need a calculator to use the equations. We proposed four simpler equations that require only mental arithmetic and tested the hypothesis that these simpler equations would have good agreement with more complex Fencl-Stewart equations. METHODS: We reduced two complex equations for the sodium-chloride effect on base excess to one simple equation: sodium-chloride effect (meq litre(-1))=[Na(+)]-[Cl(-)]-38. We simplified the equation of the albumin effect on base excess to an equation with two constants: albumin effect (meq litre(-1))=0.25x(42-[albumin]g litre(-1)). Using 300 blood samples from critically ill patients, we examined the agreement between the more complex Fencl-Stewart equations and our simplified versions with Bland-Altman analyses. RESULTS: The estimates of the sodium-chloride effect on base excess agreed well, with no bias and limits of agreement of -0.5 to 0.5 meq litre(-1). The albumin effect estimates required log transformation. The simplified estimate was, on average, 90% of the Fencl-Stewart estimate. The limits of agreement for this percentage were 82-98%. CONCLUSIONS: The simplified equations agree well with the previous, more complex equations. Our findings suggest a useful, simple way to use the Fencl-Stewart approach to analyse acid-base disorders in clinical practice.

Continuous renal replacement therapy: does technique influence electrolyte and bicarbonate control?

BACKGROUND AND OBJECTIVES: Different techniques of continuous renal replacement therapy (CRRT) might have different effects on electrolyte and acid-base control. The aim of this study was to determine whether continuous veno-venous hemodiafiltration (CVVHDF) or continuous veno-venous hemofiltration (CVVH) achieve better control of serum sodium, potassium and bicarbonate concentrations. DESIGN: Retrospective controlled study. SETTING: Two tertiary intensive care units. PATIENTS: Critically ill patients with acute renal failure (ARF) treated with CVVHDF (n=49) or CVVH (n=50). INTERVENTIONS: Retrieval of daily morning sodium and potassium values and arterial bicarbonate levels from computerized biochemical records before and after the initiation of CRRT for up to 2 weeks of treatment. Statistical comparison of findings. MEASUREMENTS AND RESULTS: Before treatment, abnormal (high or low) values were frequently observed for sodium (65.1% for CVVHDF vs. 80.0% for CVVH; NS), potassium (45.9% vs. 34.0%; NS), and bicarbonate (73.3% vs. 68.0%; NS). After treatment, however, CVVHDF was more likely to achieve serum sodium concentrations within the normal range (74.1% vs. 62.9%; p=0.0026). Both treatments decreased the mean serum potassium concentration over the first 48 h (p=0.0059 and p<0.0001, respectively), but there was no difference in terms of the normalization of serum potassium concentration during the entire treatment period (88.3% vs. 90.5%; NS). Both treatments increased the mean arterial bicarbonate concentration over the first 48 hours (p=0.011 and p<0.0001, respectively). However, CVVH was associated with a lower incidence of metabolic acidosis (13.8% for CVVH vs. 34.5% for CVVHDF; p<0.0001) and a higher incidence of metabolic alkalosis (38.9% vs. 1.1%; p<0.0001) during the entire treatment period. CONCLUSIONS: CRRT strategies based on different techniques have a significantly different impact on sodium and bicarbonate control.

Impact of continuous veno-venous hemofiltration on acid-base balance.

BACKGROUND: Continuous veno-venous hemofiltration (CVVH) appears to have a significant and variable impact on acid-base balance. However, the pathogenesis of these acid-base effects remains poorly understood. The aim of this study was to understand the nature of acid-base changes in critically ill patients with acute renal failure during continuous veno-venous hemofiltration by applying quantitative methods of biophysical analysis (Stewart-Figge methodology). METHODS: We studied forty patients with ARF receiving CVVH in the intensive care unit. We retrieved the biochemical data from computerized records and conducted quantitative biophysical analysis. We measured serum Na+, K+, Mg2+, Cl-, HCO3-, phosphate, ionized Ca2+, albumin, lactate and arterial blood gases and calculated the following Stewart-Figge variables: Strong Ion Difference apparent (SIDa), Strong Ion Difference Effective (SIDe) and Strong Ion Gap (SIG). RESULTS: Before treatment, patients had mild acidemia (pH: 7.31) secondary to metabolic acidosis (bicarbonate: 19.8 mmol/L and base excess: -5.9 mEq/L). This acidosis was due to increased unmeasured anions (SIG: 12.3 mEq/L), hyperphosphatemia (1.86 mmol/L) and hyperlactatemia (2.08 mmol/L). It was attenuated by the alkalinizing effect of hypoalbuminemia (22.5 g/L). After commencing CVVH, the acidemia was corrected within 24 hours (pH 7.31 vs 7.41, p<0.0001). This correction was associated with a decreased strong ion gap (SIG) (12.3 vs. 8.8 mEq/L, p<0.0001), phosphate concentration (1.86 vs. 1.49 mmol/L, p<0.0001) and serum chloride concentration (102 vs. 98.5 mmol/L, p<0.0001). After 3 days of CVVH, however, patients developed alkalemia (pH: 7.46) secondary to metabolic alkalosis (bicarbonate: 29.8 mmol/L, base excess: 6.7 mEq/L). This alkalemia appeared secondary to a further decrease in SIG to 6.7 mEq/L (p<0.0001) and a further decrease in serum phosphate to 0.77 mmol/L (p<0.0001) in the setting of persistent hypoalbuminemia (21.0 g/L; p=0.56). CONCLUSIONS: CVVH corrects metabolic acidosis in acute renal failure patients through its effect on unmeasured anions, phosphate and chloride. Such correction coupled with the effect of hypoalbuminemia, results in the development of a metabolic alkalosis after 72 hours of treatment.

Continuous veno-venous hemodiafiltration or hemofiltration: impact on calcium, phosphate and magnesium concentrations.

BACKGROUND AND OBJECTIVES: Different techniques of continuous renal replacement therapy (CRRT) might have different effects on calcium, phosphate and magnesium concentrations. Accordingly, we tested whether continuous veno-venous hemodia filtration (CVVHDF) or continuous venovenous hemofiltration (CVVH) would achieve better control of these electrolytes. DESIGN: Retrospective controlled study SETTING: Two tertiary Intensive Care Units PATIENTS: Critically ill patients with acute renal failure (ARF) treated with CVVHDF (n=49) or CVVH (n=50) INTERVENTIONS: Retrieval of daily morning ionized calcium, phosphate and magnesium before and after the initiation of CRRT for up to 2 weeks of treatment. MEASUREMENTS AND RESULTS: Before treatment, both groups had a high incidence of abnormal ionized calcium concentrations (57.2% for CVVHDF vs 46.0% for CVVH; NS). After treatment, both groups showed a significant increase in serum calcium concentration over the first 48 h (p=0.041 vs p=0.0048) but hypercalcemia was more common during CVVHDF (15.3% vs 0.4%; p<0.0001). However, in both groups, hypocalcemia remained common (30.9% vs 36.7%; NS). Before treatment, abnormal serum phosphate concentrations were also common (65.1% for CVVHDF vs 78.1% for CVVH; NS). After treatment, both groups achieved a significant reduction of serum phosphate within 48 hours (p<0.0001 in both groups). There was no difference in the prevalence of abnormal phosphate levels during treatment (45.5% vs 42.4%; NS). Before treatment, both groups had a high incidence of abnormal magnesium concentrations (50.0% for CVVHDF vs 51.2% for CVVH; NS). During treatment, there was no significant change in serum magnesium concentrations during the first 48 hours or in the prevalence of abnormal magnesium concentrations (56.3% vs 63.4%; p=0.13). However CVVHDF was associated with a higher prevalence of hypomagnesemia (8.1% vs 0.4%; p<0.0001) and a lower incidence of hypermagnesemia (48.2% vs. 63.0%; p=0.0014). CONCLUSIONS: In critically ill patients with ARF, calcium, phosphate and magnesium were commonly abnormal and they were only partly corrected by CRRT. CVVH and CVVHDF had a different effect on serum magnesium concentrations.