Acute renal failure and the critically ill

Acute renal failure (ARF) is commonly encountered in the intensive care unit. It is associated with considerable morbidity and mortality. There are many possible aetiologies in the critically ill, including nephrotoxic agents, hypovolaemia, and sepsis. Whilst many classification systems for ARF exist, the RIFLE (Risk, Injury, Failure, Loss, End-stage) criteria and the Acute Kidney Injury Network (AKIN) criteria are the most commonly utilized. Many supportive therapies are employed to minimize the degree of renal injury once recognized, such as fluid resuscitation, maintenance of an adequate mean arterial pressure (with the use of inotropes if persistent hypotension despite fluid and treatment of the underlying aetiology); however, if renal failure becomes established, then renal replacement therapy (RRT) may be needed to maintain homeostasis. A number of specific renal-protective agents have been studied (i.e. dopamine); however, to date none have demonstrated a clear benefit. While there are no clear guidelines with respect to the ideal mode or intensity of RRT we will discuss pros and cons of the various bedside options.     

Chlormethiazole sedation for critically ill patients in renal failure

Chlormethiazole infusions were used successfully to provide night sedation for 10-19 nights in three patients with renal failure managed by continuous veno-venous haemofiltration with dialysis. Fluid overload has accompanied the use of this drug previously because of its low concentration. The ability to remove large amounts of fluid during haemofiltration dialysis proved to be effective in preventing this. All three patients had impaired liver function and showed evidence of chlormethiazole accumulation after 4-6 days. The combination of progressive reduction in dose and daily withdrawal of infusions prevented a major problem. Acceptance of this technique by the patients was high. Chlormethiazole may be a useful addition to the drugs available to provide sedation in well defined clinical circumstances.     

Acute renal failure and the critically ill surgical patient

Acute renal failure can occur following major surgery. Predisposing factors include massive haemorrhage, sepsis, diabetes, hypertension, cardiac disease, peripheral vascular disease, chronic renal impairment and age. Understanding epidemiology, aetiology and pathophysiology can aid effective diagnosis and management. A consensus definition for acute renal failure has recently been developed. It relates to deteriorating urine output, serum creatinine and glomerular filtration rate. In the surgical patient, precipitants are often pre-renal, although intrinsic damage and obstructed urine flow can occur. Worsening renal function results in distal organ damage. Acute renal failure is a marker of disease severity, carrying a poor prognosis if associated with deteriorating respiratory and cardiovascular function. Acute renal failure in the critically ill surgical patient exerts a massive impact on the evolution of complications and prognosis. Management relates to treating life-threatening problems, maintaining effective ventilation and circulation, removal (or reduction) of nephrotoxins and, where appropriate, establishing either renal replacement therapy or palliative care.     

Rhabdomyolysis and secondary renal failure in critically ill surgical patients

Background

Rhabdomyolysis accounts for up to 28% of the causes of posttraumatic acute renal failure requiring dialysis. Clinically significant rhabdomyolysis is poorly characterized biochemically and difficult to diagnose.

Methods

A retrospective review of all surgical, trauma, burn, and pediatric surgical patients admitted to Grady Memorial Hospital in Atlanta, GA, from January 1995, through April 2002 was performed. Patients were screened for serum creatinine, base deficit, serum creatine kinase (CK) ≥1,000, presence of myoglobinuria, or if they had a clinical diagnosis of rhabdomyolysis by an attending surgeon.

Results

The sequential addition of admission laboratory values for serum creatinine ≥1.5 mg/dL (positive predictive value [PPV] = 33%), base deficit ≤−4 (PPV = 52%), serum CK level ≥5,000 U/L (PPV = 80%), and myoglobinuria increases the ability to predict which patients will develop dialysis-requiring acute renal failure after an episode of rhabdomyolysis. Patients with maximum CK ≥5,000 are also at increased risk for persistent renal insufficiency (Cr ≥2.0 mg/dL).

Conclusions

An algorithm for testing at-risk surgical patients was developed and may aid in the early diagnosis of clinically significant rhabdomyolysis.     

Refining predictive models in critically ill patients with acute renal failure

Mortality rates in acute renal failure remain extremely high, and risk-adjustment tools are needed for quality improvement initiatives and design (stratification) and analysis of clinical trials. A total of 605 patients with acute renal failure in the intensive care unit during 1989-1995 were evaluated, and demographic, historical, laboratory, and physiologic variables were linked with in-hospital death rates using multivariable logistic regression. Three hundred and fourteen (51.9%) patients died in-hospital. The following variables were significantly associated with in-hospital death: age (odds ratio [OR], 1.02 per yr), male gender (OR, 2.36), respiratory (OR, 2.62), liver (OR, 3.06), and hematologic failure (OR, 3.40), creatinine (OR, 0.71 per mg/dl), blood urea nitrogen (OR, 1.02 per mg/dl), log urine output (OR, 0.64 per log ml/d), and heart rate (OR, 1.01 per beat/min). The area under the receiver operating characteristic curve was 0.83, indicating good model discrimination. The model was superior in all performance metrics to six generic and four acute renal failure-specific predictive models. A disease-specific severity of illness equation was developed using routinely available and specific clinical variables. Cross-validation of the model and additional bedside experience will be needed before it can be effectively applied across centers, particularly in the context of clinical trials.     

Multiorgan failure in critically ill patients

Of 1136 patients admitted consecutively to two medical-surgical intensive care units, 100 were found to have multiorgan failure, defined as failure of more than two organ systems. The average duration of stay in the intensive care units was 13.4 days. The overall death rate was 78% compared with 12.8% for patients without multiorgan failure. The most common initiating illnesses or insults were sepsis, surgery, accidental trauma and cardiogenic shock. Of potential risk factors studied, shock, sepsis, surgery, pre-existing organ disease and age over 65 years were the most common. Although sepsis occurred before or during the course of multiorgan failure in 78 patients, in only 34 was sepsis judged to be the prime insult leading to multiorgan failure. Surgery during the course of multiorgan failure had neither an adverse nor beneficial effect on outcome. The mean number of organ systems failing was 4.36 for survivors and 5.03 for nonsurvivors. The most common systems to fail were central nervous, cardiovascular and respiratory.     

Oxidative stress is increased in critically ill patients with acute renal failure

Patients with acute renal failure (ARF) experience a high mortality rate. Dysregulated inflammation and altered metabolism may increase oxidative stress in ARF patients. Thirty-eight patients who met the Program to Improve Care in Acute Renal Disease (PICARD) Study inclusion criteria underwent plasma protein oxidation and plasma cytokine measurements. For comparison, similar measurements were also performed in 21 critically ill patients without ARF, 28 patients with ESRD, and 49 healthy subjects. Plasma protein thiol oxidation was measured by spectrophotometry. Plasma protein carbonyl content and cytokine concentrations were measured by ELISA. Plasma protein thiol oxidation and carbonyl content were markedly different in ARF patients compared with healthy subjects, ESRD patients, and critically ill patients (P < 0.001 in all cases). There were significant but less marked differences in plasma protein oxidation between ESRD patients and critically ill patients compared with healthy subjects. Plasma protein thiol oxidation in ARF patients improved with dialysis (P < 0.001); however, there was significant plasma oxidant reaccumulation during the interdialytic period (P < 0.001) not due to rebound equilibration of compartmentalized solutes. Plasma proinflammatory cytokine levels were significantly higher (P < 0.05) in ARF patients and critically ill patients than in healthy subjects. Plasma protein oxidation is markedly increased in ARF patients compared with healthy subjects, ESRD patients, and critically ill patients. Increased oxidative stress may be an important target for nutritional and pharmacologic therapy in ARF patients.     

Impaired monocyte cytokine production in critically ill patients with acute renal failure

BACKGROUND: Plasma levels of pro- and anti-inflammatory cytokines are predictive of mortality in patients with acute renal failure (ARF). Anti-inflammatory strategies are postulated to be beneficial in treatment. However, there are few studies simultaneously examining monocyte cytokine production and plasma cytokine levels in patients with ARF. METHODS: Study populations consisted of 20 critically ill patients with ARF, 19 critically ill patients without ARF (CRIT ILL), 28 healthy subjects (HS), 19 patients with chronic kidney disease (CKD), and 15 patients with end-stage renal disease (ESRD). Monocyte intracellular content of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8, and tumor necrosis factor-alpha (TNF-alpha) was determined by flow cytometry in whole blood. Plasma interleukin 6 and TNF-alpha concentrations were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: At baseline, there were no differences in intracellular monocyte cytokine levels between groups. After lipopolysaccaride stimulation, monocyte production of IL-1beta, TNF-alpha, and IL-6 in ARF patients was reduced by 41%, 84%, and 45%, respectively, compared to healthy subjects (P < 0.01 in each case), and similarly reduced compared to CKD and ESRD patients, and were similar to CRIT ILL patients. Plasma IL-6 levels were significantly higher in ARF patients than healthy subjects, CKD, and ESRD patients (all P < 0.001). CONCLUSION: Critically ill patients with acute renal failure have impaired monocyte cytokine production and elevated plasma cytokine levels in a pattern that closely resembles critically ill patients without ARF, and that is dissimilar to CKD and ESRD patients.     

Acute acalculous cholecystitis in critically ill patients

BACKGROUND: Acute acalculous cholecystitis (AAC) is a serious complication of critical illness. We evaluated the underlying diseases, clinical and diagnostic features, severity of associated organ failures, and outcome of operatively treated AAC in a mixed ICU patient population. METHODS: The data of all ICU patients who had operatively confirmed AAC during their ICU stay between 1 January 2000 and 31 December 2001 were collected from the hospital records and the intensive care unit's data management system for predetermined variables. RESULTS: Thirty-nine (1%) out of 3984 patients underwent open cholecystectomy for AAC during the two-year period. Infection was the most common admission diagnosis, followed by cardiovascular surgery. The mean APACHE II score on admission was 25, and 64% of the patients had three or more failing organs on the day of cholecystectomy. The mean length of ICU stay before cholecystectomy was 8 days, and the mean total length of ICU stay was 19 days. Most patients (85%) received norepinephrine infusion, and 90% suffered respiratory failure before cholecystectomy. Hospital mortality was 44%. The non-survivors had higher Sequential Organ Failure Assessment (SOFA) scores on the day of cholecystectomy compared to the survivors (12.9 vs. 9.5, P = 0.007). CONCLUSION: Acute acalculous cholecystitis was associated with severe illness, infection, long ICU stay, and multiple organ failure. Mortality was related to the degree of organ failure. Prompt diagnosis and active treatment of AAC can be life-saving in these patients.     

Unrecognized renal damage in critically ill patients

INTRODUCTION: The objective of this study was to evaluate the percentage of unrecognized renal damage in patients with normal creatinine and urea in serum and normal creatinine clearance and to evaluate the usefulness of various proteins and enzymes as supplementary procedures for the investigation of renal function. MATERIAL AND METHODS: Forty critically ill male patients (APACHE II-score > 20, injury severity score > 15) were daily screened for a period of five days. In the 1st group there were 30 patients with normal creatinine and urea in serum and with normal creatinine clearances. In the second group there were ten patients with increased values of these parameters. The base-line condition of all patients and any changes in hemodynamic, nutrition and ventilation were noted. Clearances of inulin, para-aminohippuric acid, and creatinine were measured and the Cockcroft-Gault equation was calculated daily for a period of five days. Excretion of alpha-1-microglobulin. Tamm-Horsfall-protein, alanine aminopeptidase, angiotensinase A, albumin and immunoglobulin G were also measured daily. RESULTS: 21 Patients of group 1 and all patients of group 2 showed the expected correlation between the routine parameters of creatinine and urea in serum and the level of protein and enzyme excretion. Nine patients of group 1 (30%) showed normal glomerular filtration rates but pathological excretion fractions of all proteins and enzymes. CONCLUSIONS: Although all routine parameters of renal function (creatinine and urea in serum, creatinine clearance both by 24-h collection period and from the Cockcroft-Gault equation), and additionally inulin and para-aminohippuric acid clearance were measured, no references on tubular and glomerular damage were found in 30% of the investigated patients.     

RIFLE classification is predictive of short-term prognosis in critically ill patients with acute renal failure supported by extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been utilized for critically ill patients, such as those with post-cardiotomy cardiogenic shock or life-threatening respiratory failure. Acute renal failure following ECMO support has an extremely elevated mortality rate. This study examined the outcomes of patients treated with ECMO and characterized the association between mortality and RIFLE (risk of renal failure, injury to the kidney, failure of kidney function, loss of kidney function and end-stage renal failure) classification. METHODS: This retrospective study analysed the medical records of 46 critically ill patients-most had post-cardiotomy cardiogenic shock-treated by ECMO. Sixteen patients (34.8%) were treated with both ECMO and continuous renal replacement therapies. RESULTS: The overall mortality rate was 65.2% (30/46). A progressive and significant increase (chi(2) for trend, P < 0.001) was observed for mortality based on RIFLE classification severity. The Hosmer and Lemeshow goodness-of-fit test demonstrated that the RIFLE category has a good fit. By applying the area under the receiver operating characteristic curve (AUROC), the RIFLE classification tool had good discriminative power (AUROC 0.868 +/- 0.068, P < 0.001). Cumulative survival rates at 6 months follow-up following hospital discharge differed significantly (P < 0.05) for non-ARF vs RIFLE-I and RIFLE-F, and RIFLE-R vs RIFLE-F. CONCLUSION: This investigation confirms that the prognosis for critically ill patients supported by ECMO is grave. The RIFLE category is a simple, reproducible and easily applied evaluation tool with good prognostic capability that might generate objective information for patient families and physicians and supplements the clinical judgment of prognosis.     

Identifying critically ill patients at high risk for developing acute renal failure: a pilot study

BACKGROUND: Acute renal failure (ARF) occurs commonly in the intensive care unit (ICU), but predicting which patients will develop ARF is difficult. We set out to determine which risk factors would predict the development of ARF in critically ill patients who are admitted to the ICU without ARF. METHODS: From August 2002 to April 2003, we enrolled medical-surgical ICU admissions into a cohort using a sampling tool based on their risk factor (RF) profile. The risk factors we identified were separated into 3 categories: chronic major, chronic minor, and acute RFs. Combinations of these RFs were used to create a sampling tool and identify patients to enroll into our cohort. Patients with end-stage renal disease and ARF upon admission to the ICU were excluded. RESULTS: We enrolled 194 patients over a 14-month period. The mean age of the cohort was 64.6 +/- 14.7 years. The percentage of Caucasians, African Americans, and Hispanics was 40.7%, 50.5%, and 3.6%, respectively. In a univariate analysis of the entire cohort, increasing APACHE II quartile, increased A-a gradient, presence of systemic inflammatory response syndrome (SIRS), decreased levels of serum albumin, and presence of active cancer predicted ARF. In a multiple logistic regression analysis, decreased serum albumin (high levels of serum albumin were protective), increased A-a gradient, and cancer were associated with development of ARF (OR 2.17, 1.04, and 2.86, respectively). CONCLUSION: Decreased levels of serum albumin concentration, increased A-a gradient, and presence of active cancer predict which patients who are admitted to the ICU will develop ARF.     

Outcomes and APACHE II predictions for critically ill patients with acute renal failure requiring dialysis

BACKGROUND: Despite the widespread availability of dialytic and intensive care unit technology, the probability of early mortality in critically ill patients with acute renal failure (ARF) is still high, and the evaluation of the patients' prognosis has been difficult. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score is a reliable indicator of severity of illness and likelihood of survival in critically ill patients with ARF. We have attempted to determine whether the APACHE II scoring system can be used to predict prognosis. METHODS: A retrospective cohort study evaluated the medical records of 100 consecutive patients in intensive care units with acute renal failure who required dialysis from January 1997 through December 1998. RESULTS: Of the 100 patients studied, 65 were men and 35 were women. The mean age of survivors and nonsurvivors was 59.4 +/- 20.3 years and 58.3 +/- 20.0 years. The overall mortality rate was 71%. There were no significant differences between survivors and nonsurvivors in age, gender, or indication for dialysis. The cause of death in the majority of patients was related to higher APACHE II score during the 24 hours immediately preceding the initiation of acute hemodialysis, and carry mortality rates exceeding 85% with an APACHE II score of 24 or higher. CONCLUSION: We conclude that mortality rate for acute renal failure in intensive care unit patients continues to be high. The use of the APACHE II score determined at the time of initiation of dialysis for patients with ARF is a statistically significant predictor of patient survival. There is a significant trend with APACHE II score for outcome.     

Hyperglycemia in critically ill patients: clinical implications for treatment

Hyperglycemia is frequent during critical illness and is perceived by the clinician as part of the systemic metabolic response to stress. Of all patients with "stress hyperglycemia" only one third are known to have diabetes mellitus. Previous studies reported that patients presenting hyperglycemia during acute illness have an increased risk for nosocomial infections. Morbidity and mortality also increases in patients with myocardial infarction or stroke who develop hyperglycemia. Contemporary medical practice states that hyperglycemia under these conditions should only be treated with insulin if blood glucose levels are > 200 mg/dl. A recent trial showed that intensive insulin treatment of critically ill patients in the intensive care unit with the goal of maintaining blood glucose levels between 80 and 110 mg/dl significantly reduced morbidity and mortality without significant risk of hypoglycemia. These benefits of insulin treatment are not yet well understood, but some pathophysiological evidence suggests that hyperglycemia contributes to perpetuate the systemic proinflammatory response, and insulin--a natural endogenous hormone that has a major role in the intermediary metabolism--participates actively in the systemic anti-inflammatory response. As a result of these findings, we recommend that hyperglycemia during critical illness should be treated with insulin, in order to achieve blood glucose levels in a normal range, regardless of whether or not these patients have diabetes mellitus.     

Urinary excretion of vitamin A in critically ill patients complicated with acute renal failure

OBJECTIVE: Study the possible excretion of vitamin A in urine of critically ill patients complicated with acute renal failure. PATIENTS AND METHODS: Nine Intensive Care Unit patients, age 71.2 +/- 15.7 (mean +/- SD) with acute renal failure were studied. Urinary retinol, creatinine, protein, albumin, and serum creatinine were measured. RESULTS: All patients excreted retinol in urine; individual values ranged from 0.007 to 0.379 micromol retinol/mmol creatinine. There was no correlation of urinary retinol/creatinine ratio with serum creatinine or with urinary protein/creatinine and albumin/creatinine ratios. CONCLUSION: Excretion of retinol in urine may be indicative of acute renal failure in critically ill patients.