Horng-Ruey Chua

Clinical review: Volume of fluid resuscitation and the incidence of acute kidney injury - a systematic review

Intravenous fluids are widely administered to maintain renal perfusion and prevent acute kidney injury (AKI). However, fluid overload is of concern during AKI. Using the Pubmed database (up to October 2011) we identified all randomised controlled studies of goal-directed therapy (GDT)-based fluid resuscitation (FR) reporting renal outcomes and documenting fluid given during perioperative care. In 24 perioperative studies, GDT was associated with decreased risk of postoperative AKI (odds ratio (OR) = 0.59, 95% confidence interval (CI) = 0.39 to 0.89) but additional fluid given was limited (median: 555 ml). Moreover, the decrease in AKI was greatest (OR = 0.47, 95% CI = 0.29 to 0.76) in the 10 studies where FR was the same between GDT and control groups. Inotropic drug use in GDT patients was associated with decreased AKI (OR = 0.52, 95% CI = 0.34 to 0.80, P = 0.003), whereas studies not involving inotropic drugs found no effect (OR = 0.75, 95% CI = 0.37 to 1.53, P = 0.43). The greatest protection from AKI occurred in patients with no difference in total fluid delivery and use of inotropes (OR = 0.46, 95% CI = 0.27 to 0.76, P = 0.0036). GDT-based FR may decrease AKI in surgical patients; however, this effect requires little overall FR and appears most effective when supported by inotropic drugs.

Plasma-Lyte 148 vs 0.9% saline for fluid resuscitation in diabetic ketoacidosis.

PURPOSE The purpose of the study was to determine the effects of Plasma-Lyte 148 (PL) vs 0.9% saline (NS) fluid resuscitation in diabetic ketoacidosis (DKA). METHODS A multicenter retrospective analysis of adults admitted for DKA to the intensive care unit, who received almost exclusively PL or NS infusion up until 12 hours, was performed. RESULTS Nine patients with PL and 14 patients with NS were studied. Median serum bicarbonate correction was higher in the PL vs NS groups at 4 to 6 hours (8.4 vs 1.7 mEq/L) and 6 to 12 hours (12.8 vs 6.2 mEq/L) from baseline (P < .05). Median standard base excess improved by 10.5 vs 4.2 mEq/L at 4 to 6 hours and by 16.0 vs 9.1 mEq/L at 6 to 12 hours in the PL and NS groups, respectively (P < .05). Chloride levels increased significantly in the NS vs PL groups over 24 hours. Potassium levels were lower at 6 to 12 hours in the PL group. Mean arterial blood pressure was higher at 2 to 4 hours in the PL group, whereas cumulative urine output was lower at 4 to 6 hours in the NS group. There were no differences in glycemic control or duration of intensive care unit stay. CONCLUSION Patients with DKA resuscitated with PL instead of NS had faster initial resolution of metabolic acidosis and less hyperchloremia, with a transiently improved blood pressure profile and urine output.

Circuit lifespan during continuous renal replacement therapy for combined liver and kidney failure

PURPOSE To evaluate circuit lifespan (CL) and bleeding risk during continuous renal replacement therapy (CRRT), in combined liver and renal failure. METHODS Single-center retrospective analysis of adults with acute liver failure or decompensated cirrhosis who received CRRT, without anticoagulation or with heparinization in intensive care unit. RESULTS Seventy-one patients with 539 CRRT circuits were evaluated. Median overall CL was 9 (6-16) hours. CL was 12 (7-24) hours in 51 patients never anticoagulated for CRRT. In 20 patients who subsequently received heparinization, CL was 7 (5-11) hours without anticoagulation, which did not improve with systemic or regional heparinization (P = .231), despite higher peri-circuit activated partial thromboplastin time (APTT) and heparin dose. Using multivariate linear regression, patients with higher baseline APTT or serum bilirubin, or who were not mechanically ventilated, had longer CL (P < .05). Additionally, peri-circuit thrombocytopenia (P < .0001) or higher international normalized ratio (P < .05) predicted longer CL. Of 71 patients, 33 had significant bleeding events. Using multivariate logistic regression, patients with higher baseline APTT, vasoactive drug use >24 hours, or thrombocytopenia, had more bleeding complications (P < .05). Decreasing platelet counts (especially <50 × 10(9)/mm(3)) had an incremental effect on CL (P < .0001). CONCLUSION CRRT CL is short in patients with liver failure despite apparent coagulopathy. Thrombocytopenia predicts longer CL and bleeding complications.

Phoxilium vs Hemosol-B0 for continuous renal replacement therapy in acute kidney injury☆

PURPOSE This study aimed to compare the biochemical effects of Phoxilium (containing phosphate at 1.2 mmol/L; Gambro Lundia AB, Lund, Sweden) and Hemosol-B0 (Gambro Lundia AB) as dialysate and/or replacement fluid during continuous renal replacement therapy (CRRT). METHODS We examined serum biochemistry in critically ill patients for 42 hours of Phoxilium administration for the prevention of hypophosphatemia during CRRT and compared them with corresponding results in random historical controls who received Hemosol-B0. RESULTS We studied 15 patients in each arm (Phoxilium vs Hemosol-B0). Respective median ages were 57 (49-68) and 64 (57-67) years. Baseline patient illness severity scores, prescribed CRRT effluent rates, and cumulative phosphate intakes were comparable. After 36 to 42 hours of Phoxilium administration, serum phosphate levels increased from 0.95 (0.81-1.13) to 1.44 (1.23-1.78) mmol/L, in contrast to the decline from 1.71 (1.09-2.00) to 0.83 (0.55-1.59) mmol/L with Hemosol-B0 (P=.0001). Serum ionized calcium levels decreased from 1.27 (1.22-1.37) to 1.12 (1.06-1.21) mmol/L with Phoxilium, compared with an increase from 1.09 (0.90-1.19) to 1.20 (1.16-1.25) mmol/L with Hemosol-B0 (P<.0001). Serum bicarbonate, base excess levels, and effective strong ion difference decreased with Phoxilium and were lower than those with Hemosol-B0 at 36 to 42 hours (P<.05). CONCLUSION Phoxilium effectively prevented hypophosphatemia during CRRT but was associated with relative metabolic acidosis and hypocalcemia compared with Hemosol-B0 use.

Extended Renal Outcomes with Use of Iodixanol versus Iohexol after Coronary Angiography

The impact of isoosmolar versus low-osmolar contrast media (CM) administration on contrast-induced acute kidney injury (CI-AKI) and extended renal dysfunction (ERD) is unclear. We retrospectively examined incidences of CI-AKI and ERD in patients who received iodixanol (isoosmolar) versus iohexol (low-osmolar) during angiography for cardiac indications. Of 713 patients, 560 (cohort A), 190 (cohort B), and 172 (cohort C) had serum creatinine monitored at 3 days, 30 days, and 6 months after angiography, respectively. 18% of cohort A developed CI-AKI, which was more common with iodixanol than iohexol (22% versus 13%, P = 0.006). However, patients given iodixanol were older with lower baseline estimated glomerular filtration rates (eGFR). On multivariate analysis, independent associations with higher CI-AKI risk include age >65 years, female gender, cardiac failure, ST-elevation myocardial infarction, intra-aortic balloon pump, and critical illness, but not CM type, higher CM load, or eGFR < 45 mL/min/1.73 m2. 32% of cohort B and 34% of cohort C had ERD at 30 days and 6 months, while 44% and 41% of subcohorts had ERD at 90 days and 1 year, respectively. CI-AKI, but not CM type, was associated with medium- and longer-term ERD, with 3-fold higher risk. Advanced age, emergent cardiac conditions, and critical illness are stronger predictors of CI-AKI, compared with CM-related factors. CI-AKI predicts longer-term ERD.

Nutritional Management of Patients Treated with Continuous Renal Replacement Therapy

Continuous renal replacement therapy (CRRT) is commonly performed in critically ill patients with acute kidney injury or end-stage renal disease due to better hemodynamic stability. It has greatly facilitated nutritional support in these patients by efficient volume and azotemic control, but with certain caveats. Determination of energy expenditure can be confounded by CRRT, and buffers used in CRRT fluids can be metabolized and contribute to carbohydrate load. Prolonged CRRT induces heat dissipation and negative energy transfer, and blood-membrane incompatibility and membrane protein adsorption may worsen protein catabolism. More specifically, glucose balance may be disrupted, affecting glycemic control and calorie intake. Amino acids, vitamins and trace elements can be lost selectively and in variable proportions, leading to negative nutrient balance. Electrolyte profiles need to be monitored and replaced with strict protocols. Nutritional losses can be supplemented which may improve clinical outcomes. An understanding of these mechanisms is essential to healthcare providers.

Biochemical Effects of Phosphate-Containing Replacement Fluid for Continuous Venovenous Hemofiltration

Aims: To examine biochemical effects of phosphate-containing replacement fluid (Phoxilium®) for continuous venovenous hemofiltration (CVVH). Methods: Retrospective comparison of respective serum biochemistry with sequential use of Accusol™ and Phoxilium, each over 48 h of CVVH. Results: We studied 15 critically ill patients. Accusol was switched to Phoxilium after 5 (4–8) days of CVVH. Respective serum biochemistry after 36–42 h of Accusol versus Phoxilium were: phosphate 1.02 (0.82–1.15) versus 1.44 (1.23–1.78) mmol/l, ionized calcium 1.28 (1.22–1.32) versus 1.12 (1.06–1.21) mmol/l, bicarbonate 24 (23–25) versus 20 (19–22) mmol/l, base excess 0 (–2 to 1) versus –4 (–6 to –3) mmol/l (p < 0.001). Cumulative phosphate intakes during respective periods were 69.6 (56.6–76.6) versus 67.2 (46.6–79.0) mmol (p = 0.45). Plasma strong ion differences were narrower with Phoxilium (p < 0.05), with similar strong ion gaps. No additional intravenous phosphate was given during Phoxilium use. Seven patients had serum phosphate >1.44 mmol/l. Conclusions: Phoxilium versus Accusol use during CVVH effectively prevented hypophosphatemia but contributed to mild hyperphosphatemia, and is associated with relative hypocalcemia and metabolic acidosis.

Clinically manifest thromboembolic complications of femoral vein catheterization for continuous renal replacement therapy.

PURPOSE The safety of femoral vein (FV) catheterization for continuous renal replacement therapy is uncertain. We sought to determine the incidence of clinically manifest venous thromboembolism (VTE) in such patients. METHODS We retrospectively studied patients with femoral high flow catheters (≥ 13F) (December 2005 to February 2011). Discharge diagnostic codes were independently screened for VTE. The incidence of VTE was also independently similarly assessed in a control cohort of patients ventilated for more than 2 days (January 2011 to December 2011) in the same intensive care unit (ICU). RESULTS We studied 380 patients. Their mean age was 61 years, and 59% were male. The mean Acute Physiology and Chronic Health Evaluation III score was 84; average duration of continuous renal replacement therapy was 74 hours, and 232 patients (61%) survived to hospital discharge with an average length of hospital stay of 22 days. Only 5 patients (1.3%) had clinically manifest VTE after FV catheterization. In the control cohort of 514 ICU patients, the incidence of VTE was 4.4% (P < .05 compared with FV group). CONCLUSION The incidence of clinically manifest VTE after FV catheterization with high flow catheters is low and lower to that seen in general ICU patients.

Epinephrine and short-term survival in cardiogenic shock: an individual data meta-analysis of 2583 patients

AbstractObjectiveCatecholamines have been the mainstay of pharmacological treatment of cardiogenic shock (CS). Recently, use of epinephrine has been associated with detrimental outcomes. In the present study we aimed to evaluate the association between epinephrine use and short-term mortality in all-cause CS patients. DesignWe performed a meta-analysis of individual data with prespecified inclusion criteria: (1) patients in non-surgical CS treated with inotropes and/or vasopressors and (2) at least 15% of patients treated with epinephrine administrated alone or in association with other inotropes/vasopressors. The primary outcome was short-term mortality.Measurements and resultsFourteen published cohorts and two unpublished data sets were included. We studied 2583 patients. Across all cohorts of patients, the incidence of epinephrine use was 37% (17–76%) and short-term mortality rate was 49% (21–69%). A positive correlation was found between percentages of epinephrine use and short-term mortality in the CS cohort. The risk of death was higher in epinephrine-treated CS patients (OR [CI] = 3.3 [2.8–3.9]) compared to patients treated with other drug regimens. Adjusted mortality risk remained striking in epinephrine-treated patients (n = 1227) (adjusted OR = 4.7 [3.4–6.4]). After propensity score matching, two sets of 338 matched patients were identified and epinephrine use remained associated with a strong detrimental impact on short-term mortality (OR = 4.2 [3.0–6.0]).ConclusionsIn this very large cohort, epinephrine use for hemodynamic management of CS patients is associated with a threefold increase of risk of death.

Metabolic Aspects of CRRT

Acidosis is common in patients with AKI in the ICU and often associated with acidemia. It is typically secondary to the accumulation of lactate, chloride and unmeasured anions. Its correction appears desirable and can be more reliably and safely achieved with CRRT. Use of bicarbonate-based fluids is safest as the initial approach. However, lactate- and citrate-buffered fluids can also correct acidosis if appropriately metabolized by the liver and other key organs. CRRT can also be used to correct extreme acidosis in the absence of a major degree of renal impairment. As CRRT controls volume status easily, it would additionally enable bicarbonate infusion to occur for more rapid correction of acidemia.