A Prospective, Randomized, Multicenter Trial Comparing Lactated Ringer's Alone or With 5% Albumin for Resuscitation of Large Burns The Acute Burn ResUscitation Multicenter Prospective Trial 2 (ABRUPT2).

The purpose of this study was to confirm earlier reports that low-dose vasopressin (LDVP) analogues promote urine output in patients with hepatorenal syndrome (HRS) and to check whether this mode of therapy could also be effective in renal shutdown due to nonhepatic conditions. A prospective, open, interventional study. An intermediate-level (step-down) medical intensive care unit within a general medical ward of a large university-affiliated hospital. Eighteen successive hospitalized patients with HRS (mean age 65 +/- 13 years) and 11 patients with end-stage congestive heart failure (CHF) (mean age 81 +/- 5 years) who failed to restore urine output with conventional treatment (fluids, dopamine, and diuretics) given for at least 24 h. The patients received LDVP (1 IU h-1) continuously in addition to the conventional treatment. Urine output and creatinine clearance every 24 h. In the HRS group, before treatment the urine output was 155 +/- 9 mL 24 -1h (mean +/- SD). After treatment with LDVP for 24, 48, and 72 h, urine output improved to 1067 +/- 87, 1020 +/- 501, and 1311 +/- 988 mL 24 -1h, respectively (P < 0.0001 for all measures; two-tailed paired t-test). In the CHF group, before treatment the urine output was 99 +/- 99 mL 24 -1h. After treatment with LDVP for 24, 48, and 72 h, this improved to 1125 +/- 994 mL 24 -1h (P = 0.0028), 1821 +/- 1300 mL 24 -1h (P = 0.004), and 2920 +/- 2423 mL 24 -1h (P = 0.0012), respectively. The improvement in urine output was not accompanied by a parallel improvement in creatinine clearance. The overall outcome did not change, and all patients except two in each group succumbed to their end-stage disease, due to nonrenal causes. LDVP is effective in restoring urine output both in HRS and in CHF. This suggests that LDVP affects mechanisms not specifically related to liver disease. LDVP may be useful in critical patients with renal shutdown whilst awaiting liver or heart transplantation.

Albumin is broadly prescribed for critically ill patients although it does not have a mortality benefit over crystalloids. One common use of albumin is to promote diuresis. Objectives To compare urine output in patients treated with furosemide with and without albumin and to assess other variables possibly associated with enhanced diuresis. A retrospective study was conducted on patients in a medical intensive care unit who received furosemide therapy as a continuous infusion with and without 25% albumin for more than 6 hours. Primary end points were urine output and net fluid loss. A total of 31 patients were included in the final analysis. Mean urine output in patients treated with furosemide alone did not differ significantly from output in patients treated with furo-semide plus albumin at 6, 24, and 48 hours: mean output, 1119 (SD, 597) mL vs 1201 (SD, 612) mL, P = .56; 4323 (SD, 1717) mL vs 4615 (SD, 1741) mL, P = .42; and 7563 mL (SD, 2766) vs 7432 (SD, 2324) mL, P = .94, respectively. Additionally, net fluid loss did not differ significantly between the 2 groups at 6, 24, and 48 hours. Higher concentrations of serum albumin did not improve urine output. The only independent variable significantly associated with enhanced urine output at 24 and 48 hours was increased fluid intake. Addition of albumin to a furosemide infusion did not enhance diuresis obtained with furosemide alone in critically ill patients.

Introduction AKI is increasingly recognized as a major complication of burn injury. No studies have specifically examined early AKI in burn patients. The purpose of this study was to examine AKI that develops within the first 7 days of burn injury. Methods Retrospective review of adults with burns &amp;gt; 20% TBSA admitted within 24 hours of injury to an adult regional ABA-verified burn center from 24/11/15 to 1/7/19. We excluded patients that died or who received palliation in the 1st 24 hours following the burn. AKI was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) urine and serum creatinine (s-Cr)-based criteria. The day of burn was defined as day 0. The intake to output ratio in the 1st 24 hours (I:O) was defined as total fluid Intake (mL/kg/%TBSA burn) / urine output (mL/kg). Sepsis was defined using the ABA criteria. Values are presented as median (1st-3rd IQR). Results We included 85 patients with age 46 (31.5–57) yrs., %TBSA burn 30 (23.5–46.9), and 34% with bronchoscopy-confirmed inhalation injury. AKI developed in 53 cases (62.4%) at 0 (0–1) days (range 0–6 days) post burn. Baseline s-Cr was 0.94 mg/dL (0.78–1.24), and peaked at 1.33 mg/dL (1.08–2.24), (P&amp;lt; 0.001). Distribution of AKI severity was 55% Stage I, 19% Stage II, 9% Stage III, and 17% Stage III requiring renal replacement therapy (RRT). No AKI cases had high voltage electrical burns, while 5 (9%) had sepsis and 5 (9%) were receiving vancomycin or an aminoglycoside prior to AKI onset. Comparison of AKI patients to NO AKI patients is shown in the table. High dose vitamin C resuscitation (HDVCR) had been utilized in 78% of the Stage III cases that required RRT. Compared to resuscitation using Ringers Lactate with or without 5% albumin (N= 61), HDVCR was used in 20 (38%) of AKI cases Vs. 4 (13%) of NO AKI cases (p=0.01). The I:O was 0.25 (0.16–0.46) in AKI and 0.19 (0.1–0.33) in NO AKI (p=0.04). Mortality was significantly higher in AKI than NO AKI (38% Vs. 9%, p=0.004) Conclusions Early AKI is highly prevalent following a major burn injury. Patients developing early AKI had significantly greater age, need for mechanical ventilation, and admission SOFA scores. HDVCR may be implicated in the development of early AKI. Applicability of Research to Practice Further study is required on HDVCR’s relationship to AKI.

Sequential nephron blockade using intravenous chlorothiazide is often used to enhance urine output in patients with inadequate response to loop diuretics. A few data exist to support this practice in critically ill infants. We included 100 consecutive patients <1 year of age who were administered intravenous chlorothiazide while receiving furosemide therapy in the cardiac ICU in our study. The primary end point was change in urine output 24 hours after chlorothiazide administration, and patients were considered to be responders if an increase in urine output of 0.5 ml/kg/hour was documented. Data on demographic, clinical, fluid intake/output, and furosemide and chlorothiazide dosing were collected. Multivariable regression analyses were performed to determine variables significant for increase in urine output after chlorothiazide administration. The study population was 48% male, with a mean weight of 4.9±1.8 kg, and 69% had undergone previous cardiovascular surgery. Intravenous chlorothiazide was initiated at 89 days (interquartile range 20-127 days) of life at a dose of 4.6±2.7 mg/kg/day (maximum 12 mg/kg/day). Baseline estimated creatinine clearance was 83±42 ml/minute/1.73 m2. Furosemide dose before chlorothiazide administration was 2.8±1.4 mg/kg/day and 3.3±1.5 mg/kg/day after administration. A total of 43% of patients were categorised as responders, and increase in furosemide dose was the only variable significant for increase in urine output on multivariable analysis (p<0.05). No graphical trends were noted for change in urine output and dose of chlorothiazide. Sequential nephron blockade with intravenous chlorothiazide was not consistently associated with improved urine output in critically ill infants.

Few works have analyzed factors associated with urine output in ADPKD patients taking tolvaptan (TVP). We selected 24-h urine samples from ADPKD patients treated withTVP. Urine osmolality/creatinine ratio was used as estimator of urinary osmolar load. We included 127 urine samples from 61 patients. After TVP, urine output doubled with a parallel reduction in urine solute concentration. However, when expressed as urine solute/creatinine ratios, no significant changes were observed. Daily osmolar load and osmolality/creatinine ratio did not change significantly. Before TVP, urine output was positively correlated with body weight and urine osmolality/creatinine ratio and negatively with eGFR, urine morning osmolality, and 24-h urine-calculated osmolality. After TVP, urine output was positively correlated with body weight, eGFR and negatively with age. There was a poor correlation with urine-calculated osmolality. We constructed a predictor model using mixed-effects modeling and we found that urine output was related to lower age, higher body weight, higher eGFR, and greater doses of TVP. When body weight was removed, urine output was also related to male sex and a higher daily osmolar excretion. Equation of prediction was: Urine output (mL/day) = 2771-52.9 × Age (years) + 58.4 × Weight (kg) + 18.7 × eGFR (mL/min) + 870 (if TVP = 90/30mg) + 517 (if TVP = 60/30mg). Patients taking TVP will undergo an increase about twice in urine production from baseline. Greater doses of TVP cause a progressive increase in urine production. GFR, age, and body weight are the main predictors of future urine output in patients taking TVP.

1. Hannah S. Kim, MD* 2. Francesca Costigliolo, MD† 3. Serena Bagnasco, MD† 4. Jeffrey Fadrowski, MD, MHS* 5. Rebecca L. Ruebner, MD, MSCE* 1. *Division of Pediatric Nephrology and 2. †Division of Pathology, Johns Hopkins University, Baltimore, MD A 5-year-old former 34-week girl with trisomy 21, hypothyroidism, and obstructive sleep apnea presents to the emergency department with a chief complaint of fever. She initially presented to her pediatrician 3 weeks earlier with sore throat and was diagnosed as having group A streptococcal pharyngitis. She completed 10 days of amoxicillin with resolution of sore throat. Now for the past 3 days she has had fever, chest pain, decreased enteral intake, and emesis. Review of systems is negative for diarrhea, gross hematuria, dysuria, polyuria, polydipsia, edema, weight loss, rash, arthralgia, arthritis, oral ulcers, epistaxis, and hemoptysis. She has had normal growth. She takes levothyroxine and took several doses of ibuprofen for fever over the past several weeks. There is no family history of kidney disease. She had no recent travel or sick contacts. On physical examination her weight is 45.2 lb (20.5 kg) (65th percentile); height, 46.1 in (117 cm) (62% percentile); temperature, 100.8°F (38.2°C); heart rate, 110 beats/min; respiratory rate, 24 breaths/min; oxygen saturation, 100% on room air; and blood pressure, 92/42 mm Hg (systolic 31st and diastolic 9th percentiles for age and sex). There is no pharyngeal injection or exudate. She appears well-hydrated, including moist mucous membranes. Lungs are clear to auscultation. Her abdomen is soft, nontender, and nondistended. There is no edema, and she has brisk capillary refill. She has no rash or joint swelling, erythema, or warmth. Laboratory evaluation includes a white blood cell count of 15,310/µL (15.31×109/L) with 83.6% neutrophils and 0.8% bands; hemoglobin …

Acute kidney injury (AKI) is associated with increased morbidity and mortality after liver resection. Patients with hepatocellular carcinoma (HCC) have a higher risk of AKI owing to the underlying association between hepatic and renal dysfunction. Use of the Acute Kidney Injury Network (AKIN) diagnostic criteria is recommended for patients with cirrhosis, but remains poorly studied following liver resection. We compared the prognostic value of the AKIN creatinine and urine output criteria in terms of postoperative outcomes following liver resection for HCC. All patients who underwent a liver resection for HCC from January 2010 to June 2016 were included. We used AKIN urine output and creatinine criteria to assess for AKI within 48 hours of surgery. Eighty liver resections were performed during the study period. Cirrhosis was confirmed in 80%. Median hospital stay was 9 (interquartile range 7–12) days, and 30-day mortality was 2.5%. The incidence of AKI was higher based on the urine output than on the creatinine criterion (53.8% v. 20%), and was associated with prolonged hospitalization and 30-day postoperative mortality when defined by serum creatinine (hospital stay: 11.2 v. 20.1 d, p = 0.01; mortality: 12.5% v. 0%, p < 0.01), but not urine output (hospital stay: 15.6 v. 10 d, p = 0.05; mortality: 2.3% v. 2.7%, p > 0.99). The urine output criterion resulted in an overestimation of AKI and compromised the prognostic value of AKIN criteria. Revision may be required to account for the exacerbated physiologic postoperative reduction in urine output in patients with HCC.

The aim of this study was to identify risk factors for redialysis in postoperative patients with acute renal failure (ARF) who had previously been weaned from acute dialysis. Although recovery of renal function is anticipated in patients with ARF, no data have been reported on successful weaning from acute dialysis. Retrospective observational case-control study in a 64-bed surgical ICU. Success in discontinuing dialysis was defined as cessation from dialysis for at least 30 days. A total of 304 postoperative patients who underwent acute renal replacement therapy in a surgical ICU between July 2002 and April 2005 were included. SOFA score biochemical data and renal function parameters were assessed on the day after the last session of renal replacement therapy, designated as day 0 (D0). We could wean 94 patients (30.9%) from acute dialysis for more than 5 days, and 64 of these (21.1%) were successfully weaned for at least 30days. The independent predictors for resuming dialysis within 30 days were: (a) longer duration of dialysis (OR 1.06), (b) higher SOFA score on D0 (OR 1.44), (c) oliguria (urine output <100cc/8h; OR 4.17) on D1, and (d) age over 65 years (OR 6.35). The area under the ROC curve was 0.880. Two-way analysis of variance with repeated measurements over time showed a larger decline in SOFA score and an increase in urine output in patients with successful cessation of dialysis. Kaplan-Meier analysis showed a significant difference in early resumption of dialysis between patients with or without oliguria at D0. More than two-thirds of patients weaned from postoperative acute dialysis for more than 5 days were free of dialysis for at least 30 days. Less urine output, longer duration of dialysis, age over 65 years, and higher disease severity score are predictive of a patient's redialysis after initial weaning from acute dialysis.

To investigate the circadian variation of plasma antidiuretic hormone (ADH) and urine output in patients with severe nocturia (> three times per night) and to assess the effect of oral desmopressin on nocturnal urine output in these patients. Twelve patients with severe nocturia and five age-matched controls without were assessed over 24 h (circadian sampling) during a 72-h hospital admission. Blood levels of ADH and changes of urine output were measured in the patients before and after the oral administration of desmopressin (0.2 mg, at 22.00 hours in the second day), and in the controls not treated with desmopressin. Compared with the normal control, the patients had no diurnal variation in urine output and greater nocturnal urine production, associated with a lack of nocturnal increase in ADH level. Compared with the baseline urine output, desmopressin significantly decreased night-time (23.00-08.00 hour) urine output in the patients (P < 0.05). Desmopressin significantly increased the osmolality of night-time urine (P < 0.05), and there was no systemic adverse reaction. Severe nocturia in a large proportion of elderly men with lower urinary tract symptoms is caused by nocturnal polyuria and natriuresis, because they have no nocturnal increase in ADH. These results suggest that desmopressin may be effective in decreasing nocturnal urine production in patients with severe nocturia who do not respond to conventional treatment.

Improving Outcomes From Acute Kidney Injury: Report of an Initiative

Introduction: Oxidative stress plays a major role in the pathology of hemorrhagic shock (HS). Acute kidney injury, cerebral edema (induced by increased AQP4 and NKCC1 expression) and cerebral perfusion pressure (CPP) drop are associated with high morbidity and mortality in HS. There is evidence that vasopressin is preferable to lactated Ringer's (LR) in HS. We hypothesized that terlipressin (TLP) protects the kidneys (K) and brain (B) in HS. Methods: We studied 35 female pigs (20-30 kg) in groups: sham; shock (60% reduction in blood volume-mean arterial pressure [MAP] of 40 mmHg for 30 min); LR (post-shock LR given at 3× the volume of blood removed); and TLP (2 mg of TLP given post-shock). At 60 min post-treatment, we evaluated CPP (mmHg), MAP (mmHg) and serum creatinine (Creat, mg/dl) and at 120 min post-treatment, we evaluated 2-thiobarbituric acid reactive substances (TBARS, nmol/g) (in B and K), as well as immunoblotting for AQP2, NKCC2 and Bax (in K); and AQP4, NKCC1 and Bax (in B). Results: Data are mean±SEM. MAP was markedly lower in Shock and LR than in Sham and TLP (49 ± 4.8 and 55 ± 2.9 vs. 71 ± 2.1 and 63 ± 3.0, P < 0.05). TLP treatment completely inhibited the decrease of CPP observed in Shock and LR (59 ± 2.6 vs. 45 ± 4.4 and 47 ± 2.9, P < 0.05) and was similar to Sham (65 ± 1.6). The TBARSB level was higher in Shock and LR groups than in Sham group (264 ± 46 and 308 ± 96 vs. 34.7 ± 5.7, P < 0.05). Although significantly different from Shock and LR groups, the TBARSB level observed for the TLP group (137 ± 9.5) differed significantly from the Sham group. Serum levels of creat were higher in Shock, LR and TLP groups than in Sham group (1.5 ± 0.08, 1.0 ± 0.09 and 1.3 ± 0.07 vs. 0.9 ± 0.07, P < 0.05). The TBARSk level was higher in Shock, LR and TLP groups than in Sham group (106 ± 23, 163 ± 62 and 108 ± 31 vs. 28.5 ± 1.1, P < 0.05). Expression of BaxB was markedly higher in shock and LR groups than in Sham (190 ± 30% and 154 ± 16% vs. 97 ± 2.5%, P < 0.05). TLP treatment completely inhibited the upregulation of BaxB (102 ± 2.6%). Similar, expression of Baxk was markedly higher in shock and LR groups than in Sham group (139 ± 5.1% and 130 ± 10% vs. 99 ± 0.6%, P < 0.05). TLP treatment completely inhibited the upregulation of BaxB (97.5 ± 8.5%). AQP2 expression was comparable in Sham and TLP pigs (97 ± 3.0% and 107 ± 5.0%) and was significantly lower in Shock (22 ± 2.5%) and LR (43 ± 12%) compared to Sham and TLP groups ( P < 0.05). NKCC2 expression was lower in Shock and LR pigs than in Sham and TLP pigs (27.5 ± 4.8% and 50 ± 21% vs. 102 ± 1.7% and 92.5 ± 12.5%, P < 0.05). Shock-induced increases in AQP4 (217%) and NKCC1 (237%) were reversed by TLP but not by LR. Conclusions: TLP-related protection appears to depend on sodium/water transporter regulation and be attributable, in part, to inhibition of oxidant injury.

Sirs,The article by Hobbs and coworkers [1] provides scientificevidence for what we believe is a common clinical practice:the use of rasburicase in hyperuricemic newborns withacute kidney injury (AKI).These authors retrospectively reviewed the charts of 7hyperuricemic infants with AKI, successfully treated with asingle dose of rasburicase (0.17±0.04 mg/kg).Duringthelastfewyearswealsoexperiencedtheefficacyand safety of rasburicase in 10 AKI newborns (7 boys, 3girls), with a mean (± SD) body weight of 1,226 g (± 644.4),born at 29.4 weeks (± 30 days) and with a mean age atadministration of therapy of 20.2 days (± 11.5). Six of themwere of very low birth weight (VLBW) and 9 werepremature (data not published).After a single intravenous dose of rasburicase (0.2 mg/kgin 30 min) we also observed a statistically significantdecrease in serum uric acid concentration of a mean levelranging from 14.5±3.6 mg/dl to 6.6±7.5 mg/dl (p<0.002).No side effects were recorded.Hobbs and coworkers reported a significant improvementin serum creatinine and urine output on day 1 followingrasburicase [1]. The authors seem to attribute these results tothe reduction in serum uric acid as described in oncologicalpatients with tumor lysis syndrome (TLS) [2–4]. These dataare not confirmed by our study. We believe that uric acidplays a pathogenetic role in AKI secondary to TLS, while, asin the series by Hobbs et al., our patient’s uric acid increasedas a consequence of a reduction in urinary excretion, ratherthan overproduction. In fact, if we analyze each patientseparately it can be speculated that the specific therapy of theunderlying diseases, such as rehydration, is the main factorexplaining the improvement in serum creatinine and urineoutput, as evidenced by the sharp decrease in blood ureanitrogen and the improvement in urine output (in patients 1,3, and 7) after rehydration and/or resuscitation. Moreover, in2 cases (patients 2 and 4) serum creatinine remainedsignificantly high during the first week after treatment.At present, various studies have confirmed that rasburi-case is effective in reducing uric acid concentration and iswell tolerated [1, 4, 5], even in the neonatal period [3] andin premature newborns, as shown by our experience.References

Perioperative Acute Kidney Injury

Survival outcomes in older patients with different stages of acute kidney injury defined by the addition of urine output criteria.

Case Scenario: Hemodynamic Management of Postoperative Acute Kidney Injury