Hiroshi Morimatsu

Septic Acute Kidney Injury in Critically Ill Patients: Clinical Characteristics and Outcomes

Sepsis is the most common cause of acute kidney injury (AKI) in critical illness, but there is limited information on septic AKI. A prospective, observational study of critically ill patients with septic and nonseptic AKI was performed from September 2000 to December 2001 at 54 hospitals in 23 countries. A total of 1753 patients were enrolled. Sepsis was considered the cause in 833 (47.5%); the predominant sources of sepsis were chest and abdominal (54.3%). Septic AKI was associated with greater aberrations in hemodynamics and laboratory parameters, greater severity of illness, and higher need for mechanical ventilation and vasoactive therapy. There was no difference in enrollment kidney function or in the proportion who received renal replacement therapy (RRT; 72 versus 71%; P = 0.83). Oliguria was more common in septic AKI (67 versus 57%; P < 0.001). Septic AKI had a higher in-hospital case-fatality rate compared with nonseptic AKI (70.2 versus 51.8%; P < 0.001). After adjustment for covariates, septic AKI remained associated with higher odds for death (1.48; 95% confidence interval 1.17 to 1.89; P = 0.001). Median (IQR) duration of hospital stay for survivors (37 [19 to 59] versus 21 [12 to 42] d; P < 0.0001) was longer for septic AKI. There was a trend to lower serum creatinine (106 [73 to 158] versus 121 [88 to 184] mumol/L; P = 0.01) and RRT dependence (9 versus 14%; P = 0.052) at hospital discharge for septic AKI. Patients with septic AKI were sicker and had a higher burden of illness and greater abnormalities in acute physiology. Patients with septic AKI had an increased risk for death and longer duration of hospitalization yet showed trends toward greater renal recovery and independence from RRT.

A comparison of observed versus estimated baseline creatinine for determination of RIFLE class in patients with acute kidney injury

BACKGROUND The RIFLE classification scheme for acute kidney injury (AKI) is based on relative changes in serum creatinine (SCr) and on urine output. The SCr criteria, therefore, require a pre-morbid baseline value. When unknown, current recommendations are to estimate a baseline SCr by the MDRD equation. However, the MDRD approach assumes a glomerular filtration rate of approximately 75 mL/min/1.73 m(2). This method has not been validated. METHODS Data from the Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) study, a prospective observational study from 54 ICUs in 23 countries of critically ill patients with severe AKI, were analysed. The RIFLE class was determined by using observed (o) pre-morbid and estimated (e) baseline SCr values. Agreement was evaluated by correlation coefficients and Bland-Altman plots. Sensitivity analysis by chronic kidney disease (CKD) status was performed. RESULTS Seventy-six percent of patients (n = 1327) had a pre-morbid baseline SCr, and 1314 had complete data for evaluation. Forty-six percent had CKD. The median (IQR) values were 97 micromol/L (79-150) for oSCr and 88 micromol/L (71-97) for eSCr. The oSCr and eSCr determined at ICU admission and at study enrolment showed only a modest correlation (r = 0.49, r = 0.39). At ICU admission and study enrolment, eSCr misclassified 18.8% and 11.7% of patients as having AKI compared with oSCr. Exclusion of CKD patients improved the correlation between oSCr and eSCr at ICU admission and study enrolment (r = 0.90, r = 0.84) resulting in 6.6% and 4.0% being misclassified, respectively. CONCLUSIONS While limited, estimating baseline SCr by the MDRD equation when pre-morbid SCr is unavailable would appear to perform reasonably well for determining the RIFLE categories only if and when pre-morbid GFR was near normal. However, in patients with suspected CKD, the use of MDRD to estimate baseline SCr overestimates the incidence of AKI and should not likely be used. Improved methods to estimate baseline SCr are needed.

Unmeasured anions in critically ill patients: Can they predict mortality?

ObjectiveTo determine whether base excess, base excess caused by unmeasured anions, and anion gap can predict lactate in adult critically ill patients, and also to determine whether acid-base variables can predict mortality in these patients. DesignRetrospective study. SettingAdult intensive care unit of tertiary hospital. PatientsThree hundred adult critically ill patients admitted to the intensive care unit. InterventionsRetrieval of admission biochemical data from computerized records, quantitative biophysical analysis of data with the Stewart-Figge methodology, and statistical analysis. Measurements and Main ResultsWe measured plasma Na+, K+, Mg2+, Cl−, HCO3−, phosphate, ionized Ca2+, albumin, lactate, and arterial pH and Paco2. All three variables (base excess, base excess caused by unmeasured anions, anion gap) were significantly correlated with lactate (r2 = .21, p < .0001; r2 = .30, p < .0001; and r2 = .31. p < .0001, respectively). Logistic regression analysis showed that the area under the receiver operating characteristic (AUROC) curves had moderate to high accuracy for the prediction of a lactate concentration >5 mmol/L: AUROC curves, 0.86 (95% confidence interval [CI], 0.78–0.94), 0.86 (95% CI, 0.78–0.93), and 0.85 (95% CI, 0.77–0.92), respectively.Logistic regression analysis showed that hospital mortality rate correlated significantly with Acute Physiology and Chronic Health Evaluation (APACHE) II score, anion gap corrected (anion gap corrected by albumin), age, lactate, anion gap, chloride, base excess caused by unmeasured anions, strong ion gap, sodium, bicarbonate, strong ion difference effective, and base excess. However, except for APACHE II score, AUROC curves for mortality prediction were relatively small: 0.78 (95% CI, 0.72–0.84) for APACHE II, 0.66 (95% CI, 0.59–0.73) for lactate, 0.64 (95% CI, 0.57–0.71) for base excess caused by unmeasured anions, and 0.63 (95% CI, 0.56–0.70) for strong ion gap. ConclusionsBase excess, base excess caused by unmeasured anions, and anion gap are good predictors of hyperlactatemia (>5 mmol/L). Acid-base variables and, specifically, “unmeasured anions” (anion gap, anion gap corrected, base excess caused by unmeasured anions, strong ion gap), irrespective of the methods used to calculate them, are not accurate predictors of hospital mortality rate in critically ill patients.

Discontinuation of continuous renal replacement therapy: A post hoc analysis of a prospective multicenter observational study*

Objectives:To describe current practice for the discontinuation of continuous renal replacement therapy in a multinational setting and to identify variables associated with successful discontinuation. The approach to discontinue continuous renal replacement therapy may affect patient outcomes. However, there is lack of information on how and under what conditions continuous renal replacement therapy is discontinued. Design:Post hoc analysis of a prospective observational study. Setting:Fifty-four intensive care units in 23 countries. Patients:Five hundred twenty-nine patients (52.6%) who survived initial therapy among 1006 patients treated with continuous renal replacement therapy. Interventions:None. Measurements and Main Results:Three hundred thirteen patients were removed successfully from continuous renal replacement therapy and did not require any renal replacement therapy for at least 7 days and were classified as the “success” group and the rest (216 patients) were classified as the “repeat-RRT” (renal replacement therapy) group. Patients in the “success” group had lower hospital mortality (28.5% vs. 42.7%, p < .0001) compared with patients in the “repeat-RRT” group. They also had lower creatinine and urea concentrations and a higher urine output at the time of stopping continuous renal replacement therapy. Multivariate logistic regression analysis for successful discontinuation of continuous renal replacement therapy identified urine output (during the 24 hrs before stopping continuous renal replacement therapy: odds ratio, 1.078 per 100 mL/day increase) and creatinine (odds ratio, 0.996 per &mgr;mol/L increase) as significant predictors of successful cessation. The area under the receiver operating characteristic curve to predict successful discontinuation of continuous renal replacement therapy was 0.808 for urine output and 0.635 for creatinine. The predictive ability of urine output was negatively affected by the use of diuretics (area under the receiver operating characteristic curve, 0.671 with diuretics and 0.845 without diuretics). Conclusions:We report on the current practice of discontinuing continuous renal replacement therapy in a multinational setting. Urine output at the time of initial cessation of continuous renal replacement therapy was the most important predictor of successful discontinuation, especially if occurring without the administration of diuretics.

Intrarenal blood flow distribution in hyperdynamic septic shock: Effect of norepinephrine.

ObjectivesTo measure changes in medullary and cortical renal blood flow during experimental hyperdynamic sepsis and the effect of subsequent norepinephrine infusion on such flows. DesignExperimental animal study. SettingAnimal laboratory of university-affiliated physiology institute. SubjectsEighteen anesthetized merino sheep. InterventionsA transit-time flow probe was placed around the left renal artery. Laser Doppler flow probes were inserted in the left renal medulla and cortex by micromanipulation to measure changes in regional intrarenal blood flow. Measurements and Main ResultsSystemic pressures, cardiac output, renal, and intrarenal blood flows were measured continuously. A bolus of Escherichia coli (7.5 × 10 9 colony forming units) was given intravenously to induce hyperdynamic sepsis. After the onset of hyperdynamic sepsis, all animals were randomly allocated to either norepinephrine (0.4 &mgr;g·kg−1·min−1 for 30 mins) or observation for 30 mins in random order. E. coli injection induced a significant decrease in mean arterial pressure (102.2 ± 15.2 mm Hg to 74.3 ± 16.1 mm Hg, p < .05) and an increase in mean cardiac output (4.60 ± 1.62 L/min to 5.93 ± 1.18 L/min, p < .05). However, renal blood flow did not change significantly (326.4 ± 139.4 mL/min to 293.1 ± 117.5 mL/min, not significant) despite a 30% increase in renal conductance (3.27 ± 1.52 to 4.13 ± 2.01 mL·min−1·mm Hg−1, p < .05). Cortical blood flow decreased by 15% (not significant) and medullary flow by 5% (not significant) during sepsis, but individual changes were unpredictable. On the other hand, norepinephrine infusion caused a significant improvement in mean arterial pressure (74.3 ± 16.1 to 105.7 ± 17.7 mm Hg, p < .05) and a further increase in cardiac output (5.93 ± 1.18 to 7.13 ± 1.52 L/min, p < .05). Mean renal blood flow also increased (293.1 ± 117.5 to 384.5 ± 168.1 mL/min, p < .05) despite decreased renal conductance (4.13 ± 2.01 to 3.73 ± 1.91 mL·min−1·mm Hg−1, p < .05). Infusion of norepinephrine significantly increased medullary blood flow by 35% compared with baseline (p < .05) and by 54% compared with untreated sepsis (p < .05), whereas the increases in cortical blood flow (16 and 53%, respectively) were not significant. ConclusionsHyperdynamic sepsis caused renal vasodilation but had limited effects on regional intrarenal blood flow. Norepinephrine infusion (0.4 &mgr;g·kg−1·min−1) during sepsis significantly increased global and medullary renal blood flow and restored renal vascular tone toward but not above normal.

The effects of continuous epidural anesthesia and analgesia on stress response and immune function in patients undergoing radical esophagectomy

We investigated whether perioperative extensive epidural block (C3-L) affects postoperative immune response in patients undergoing radical esophagectomy. Patients undergoing radical esophagectomy were randomly assigned to either general anesthesia with continuous epidural infusion via 2 epidural catheters that was continued for postoperative analgesia (group E, n = 15) or intraoperative general anesthesia and postoperative IV morphine analgesia (group G, n = 15). Plasma levels of stress hormones, cytokines, C-reactive protein (CRP), leukocyte counts, and distribution of lymphocyte subsets were assessed before and after surgery and on postoperative days (PODs) 1 and 3. In comparison with group E, significant increases in plasma epinephrine level at the end of surgery (P < 0.05) and norepinephrine level at the end of surgery (P < 0.01) and on POD1 (P < 0.01) and POD3 (P < 0.01) and significant decrease in cluster of differentiation (CD4/CD8 ratio) at the end of surgery (P < 0.05) were observed in group G. However, there were no significant differences in other variables between groups. In both groups, plasma cortisol, adrenocorticotropic hormone, interleukin (IL)-1β, IL-6, IL-10, and CRP levels were increased after surgery (each group P < 0.01) and IL-1β, IL-6, IL-10, and CRP were still increased on POD1 and POD3 (each change, each group P < 0.01). Leukocyte counts were increased on POD1 (each group P < 0.05) and POD3 (each group P < 0.01). The proportion of lymphocytes decreased from the end of surgery to POD3 (each group P < 0.01). The proportion of B cells was increased on POD1 (each group P < 0.01); that of natural killer cells was decreased at POD1 and POD3 (each group P < 0.01). We conclude that tissue damage and inflammation apparently overcome the effects of extensive epidural block on stress response and immune function in radical esophagectomy.

Comparison of point-of-care versus central laboratory measurement of electrolyte concentrations on calculations of the anion gap and the strong ion difference.

Background Clinicians calculate the anion gap (AG) and the strong ion difference (SID) to make acid-base diagnoses. The technology used is assumed to have limited impact. The authors hypothesized that different measurement technologies markedly affect AG and SID values. Methods SID and AG were calculated using values from the point-of-care blood gas and electrolyte analyzer and the central hospital laboratory automated blood biochemistry analyzer. Simultaneously measured plasma sodium, potassium, and chloride concentrations were also compared. Results Mean values for central laboratory and point-of-care plasma sodium concentration were significantly different (140.4 ± 5.6 vs. 138.3 ± 5.9 mm;P < 0.0001), as were those for plasma chloride concentration (102.4 ± 6.5 vs. 103.4 ± 6.0 mm;P < 0.0001) but not potassium. Mean AG values calculated with the two different measurement techniques differed significantly (17.6 ± 6.2 mEq/l for central laboratory vs. 14.5 ± 6.0 mEq/l for point-of-care blood gas analyzer;P < 0.0001). Using the Stewart-Figge methodology, SID values also differed significantly (43.7 ± 4.8 vs. 40.7 ± 5.6 mEq/l;P < 0.0001), with mean difference of 3.1 mEq/l (95% limits of agreement, −3.4, 9.5 mEq/l). For 83 patients (27.6%), differences in AG values were as high as 5 mEq/l or more, and for 46% of patients whose AG value was outside the reference range with one technology, a value within normal limits was recorded with the other. Conclusions Results with two different measurement technologies differed significantly for plasma sodium and chloride concentrations. These differences significantly affected the calculated AG and SID values and might lead clinicians to different assessments of acid-base and electrolyte status.

Pre-Dilution vs. Post-Dilution during Continuous Veno-Venous Hemofiltration: Impact on Filter Life and Azotemic Control

Background/Aims: To determine the impact of replacement fluid infusion site on filter life and azotemic control during continuous veno-venous hemofiltration (CVVH). Methods:Pre-dilution CVVH was conducted from February 2001 to December 2001 and then practice was changed to post-dilution (from January 2002 to July 2002). Filter life was prospectively observed and the following data obtained for each filter: starting date and time, ending date and time, heparin use, heparin dose and protamine use. Daily creatinine, urea, INR, APTT and platelet count were also collected. Results: Forty-eight patients were studied (33 in pre-dilution and 15 in post-dilution) for a total of 309 filters (202 in pre-dilution and 107 in post-dilution). The median filter life was significantly shorter in the post-dilution period (18.0 vs. 13.0 h, p = 0.021). Multivariate linear regression analysis showed that pre-dilution was a significant independent predictor of increased filter life (p = 0.029), together with platelet count (p = 0.0035) and heparin dose (p = 0.046). There was no significant improvement in daily creatinine and/or urea reduction in the post-dilution period (% Δ creatinine: 7.9 vs. 10.2%/day, p = 0.99, urea: 5.4 vs. 9.7%/ day, p = 0.78). Conclusions: Post-dilution was associated with reduced filter life without any beneficial effect on daily changes in urea and creatinine levels. Pre-dilution appears a preferable technical approach to CVVH.

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.

End-Stage Renal Failure Patients Requiring Renal Replacement Therapy in the Intensive Care Unit: Incidence, Clinical Features, and Outcome

Aims: To study incidence, clinical features, and outcome of critically ill patients with end-stage renal failure (ESRF) requiring renal replacement therapy (RRT) in the intensive care unit (ICU) and to test the validity of severity scoring systems for these patients. Methods: Data for ESRF patients treated with RRT were collected from 81 Australian adult ICUs providing RRT. They were compared with matched controls with acute renal failure. Results: Thirty-eight ESRF patients received RRT in the ICU over 3 months. The mean APACHE II score was 21.8 (predicted mortality: 37%) and the SAPS II score 44.7 (predicted mortality: 37%). The hospital mortality was 34%. Receiver operating characteristic curves showed good discrimination ability for hospital mortality for these two scores (AUC: 0.81 for APACHE II and 0.84 for SAPS II). Using admission diagnosis and SAPS II scores, 32 ESRF patients treated with continuous RRT (CRRT) were matched to 32 acute renal failure patients also treated with CRRT. ICU mortality (22 vs. 38%) and hospital mortality (38 vs. 38%) were comparable between the two groups. Conclusions: ESRF patients requiring RRT in the ICU were relatively frequent. Severity scores could be used to predict the hospital outcome for these patients. Their mortality, when treated with CRRT, was similar to that of diagnosis- and severity-score-matched patients with acute renal failure.