Trace element and vitamin concentrations and losses in critically ill patients treated with continuous venovenous hemofiltration

OBJECTIVES: To measure the blood concentrations of a number of trace elements and vitamins in critically ill patients and examine their elimination by continuous venovenous hemofiltration (CVVH). SETTING: Intensive care unit of a tertiary institution. DESIGN: Prospective, controlled, clinical study. PATIENTS: Eight critically ill patients requiring renal replacement therapy, nine patients requiring intensive care treatment but not requiring renal replacement therapy, and nine healthy controls. INTERVENTIONS: Measurement of trace element and vitamin concentrations in blood and ultrafiltrate. MEASUREMENTS AND MAIN RESULTS: Compared with normal volunteers, critically ill patients requiring CVVH had significantly lower median blood concentrations of vitamin C, vitamin E, selenium, and zinc. During the first 24 hrs of CVVH, there were no changes in the trace element and vitamin concentrations in blood, nor were there differences between pre- and postfilter samples. Micronutrient losses in the ultrafiltrate were small or undetectable except for Vitamin C, chromium, and copper. Compared with normal volunteers, critically ill patients not requiring CVVH also had significantly lower median blood concentrations of vitamin C, vitamin E, selenium, and zinc. There were no differences between the two critically ill groups. CONCLUSIONS: The clinical significance of the reductions in blood concentrations of selenium, zinc, vitamin C, and vitamin E in critically ill patients and the ultrafiltrate losses of Vitamin C, copper, and chromium remains unclear.     

Pharmacokinetics of meropenem in critically ill patients with acute renal failure treated by continuous hemodiafiltration

A prospective, randomized, double-blind and placebo-controlled study was conducted to assess the effectiveness of i.v. administration of 6% hydroxyethyle starch solution (HES) in preventing moderate and severe ovarian hyperstimulation syndrome (OHSS) in patients in an in-vitro fertilization programme. A total of 101 women who had serum oestradiol concentrations >1500 pg/ml and/or more than 10 follicles on day of human chorionic gonadotrophin (HCG) administration were recruited into two groups: HES group (n = 51) received 1000 ml 6% HES; and the placebo group (n = 50) received 1000 ml of sodium chloride 0.9% solution at the time shortly after embryo transfer. Follow-up examinations 7 +/- 1 and 14 +/- 1 days after embryo transfer included transvaginal ultrasound (diameters of each ovary and maximum cysts, number of cysts, ascites), blood tests (serum oestradiol, progesterone, beta-HCG, C-reactive protein, blood count, plasma proteins, electrolytes, kidney function tests) and evaluation of abdominal pain, nausea, diarrhoea, abdominal swelling and weight gain. Only one moderate OHSS developed in the HES group whereas seven moderate-severe cases were observed in the placebo group (P = 0.031). Furthermore, serum oestradiol concentration, leukocyte count, increase in abdominal circumference and weight gain 14 days after embryo transfer were significantly higher in the placebo group. There were no differences between the two groups in terms of age, oestradiol concentration and number of follicles at time of HCG injection. Administration of 6% HES prevents the development of moderate-severe OHSS in risk patients.     

Pharmacokinetics of anti-infective agents in continuous hemofiltration

NEW ASSIST TECHNIQUES: Continuous hemofiltration and hemodiafiltration are two new renal replacement techniques offering continuous electrolyte regulation and hemodynamic stability in patients with multiple organ failure. These continuous techniques are being used more and more in intensive care, especially as renal replacement in case of septic shock, and probably have the additional benefit of removing toxins. EFFECT ON ANTIMICROBIALS: Little is known about the removal of drugs and in particular antimicrobials during continuous hemofiltration although both the specific pharmacokinetics of each drug and the patient's particular clinical situation plays an important role. DRUG DOSING: In the intensive care unit, knowledge of the effect of continuous hemofiltration on drug removal and pharmacokinetic profile is crucial for practical management due to the importance of avoiding infratherapeutic serum levels, or inversely toxic levels, in these seriously ill patients. Titration equations provided in most of the recent articles are helpful but usually based on a large number of parameters not always easily available in clinical practice. An approximation of the dose can be estimated from dosing guides for continuous dialysis which can be useful in avoiding poorly adapted dosage.     

Pharmacokinetics and pharmacodynamics of bumetanide in critically ill pediatric patients

This prospective, open-label, clinical trial was conducted to describe the pharmacology of bumetanide in pediatric patients with edema. Nine infants, children, and young adults with edema who were selected for diuretic therapy were studied. After a brief baseline period, each patient received parenteral bumetanide 0.2 mg/kg divided into two equal doses and administered every 12 hours. Urine excretion rate, fractional and total excretion of Na+, Cl-, and K+, creatinine clearance, and plasma and urine concentrations of bumetanide were measured at multiple intervals after drug administration. Bumetanide caused significant increases in the excretion rate of urine and each measured electrolyte. Unexpectedly, creatinine clearance increased dramatically after each dose. Adverse effects, including hypokalemia and hypochloremic metabolic alkalosis, were evident by the end of the treatment period. The plasma pharmacokinetics of bumetanide revealed mean +/- standard deviation values for total clearance and apparent volume of distribution of 3.9 +/- 2.4 mL/min/kg and 0.74 +/- 0.54 L/kg, respectively. Patients excreted an average of 34% of each dose unchanged in the urine over 12 hours. Plasma concentrations of bumetanide accurately predicted several renal effects using a link model with similar pharmacodynamic parameters in each case. Parenteral bumetanide 0.1 mg/kg administered every 12 hours produced significant beneficial and adverse effects in these critically ill pediatric patients with edema. Pharmacokinetic parameters are similar to those previously reported for infants. Plasma concentrations of bumetanide can predict effect-compartment pharmacodynamics.     

Pharmacokinetics of liposomal amphotericin B (Ambisome) in critically ill patients

The liposomal formulation of amphotericin B (AmBisome) greatly reduces the acute and chronic side effects of the parent drug. The present study describes the pharmacokinetic characteristics of AmBisome applied to 10 patients at a dose of 2.8 to 3.0 mg/kg of body weight and compares them to the pharmacokinetics observed in 6 patients treated with amphotericin B deoxycholate at the standard dose of 1.0 mg/kg. Interpatient variabilities of amphotericin B peak concentrations (Cmax) and areas under concentration-time curves (AUC) were 8- to 10-fold greater for patients treated with AmBisome than for patients treated with amphotericin B deoxycholate. At the threefold greater dose of AmBisome, median Cmaxs were 8.4-fold higher (14.4 versus 1.7 microg/ml) and median AUCs exceeded those observed with amphotericin B deoxycholate by 9-fold. This was in part explained by a 5.7-fold lower volume of distribution (0.42 liters/kg) in AmBisome-treated patients. The elimination of amphotericin B from serum was biphasic for both formulations. However, the apparent half-life of elimination was twofold shorter for AmBisome (P = 0.03). Neither hemodialysis nor hemofiltration had a significant impact on AmBisome pharmacokinetics as analyzed in one patient. In conclusion, the liposomal formulation of amphotericin B significantly (P = 0.001) reduces the volume of drug distribution, thereby allowing for greater drug concentrations in serum. The low toxicity of AmBisome therefore cannot readily be explained by its serum pharmacokinetics.     

Creatinine and urea clearance during continuous veno-venous haemofiltration in critically ill patients

A case involving an adult man with postejaculation hematuria (PEH) is described. We used transrectal color Doppler ultrasonography to evaluate periprostatic or intraprostatic vascular anomalies. We confirmed a vascular anomaly by angiography and embolized it. Periprostatic vascular anomaly may be a cause of PEH, and color Doppler ultrasonography is helpful for the initial studies of this entity.     

A primer on continuous renal replacement therapy for critically ill patients

OBJECTIVES: To characterize the multiple continuous renal replacement therapy (CRRT) techniques available for the management of critically ill adults, and to review the indications for and complications of use, principles of drug removal during CRRT, drug dosage individualization guidelines, and the influence of CRRT on patient outcomes. DATA SOURCES: MEDLINE (January 1981-December 1996) was searched for appropriate publications by using terms such as hemofiltration, ultrafiltration, hemodialysis, hemodiafiltration, medications, and pharmacokinetics; selected articles were cross-referenced. STUDY SELECTION: References selected were those considered to enhance the reader's knowledge of the principles of CRRT, and to provide adequate therapies on drug disposition. DATA SYNTHESIS: CRRTs use filtration/convection and in some cases diffusion to treat hemodynamically unstable patients with fluid overload and/or acute renal failure. Recent data suggest that positive outcomes may also be attained in patients with other medical conditions such as septic shock, multiple organ dysfunction syndrome, and hepatic failure. Age, ventilator support, inotropic support, reduced urine volume, and elevated serum bilirubin concentrations have been associated with poor outcomes. Complications associated with CRRT include bleeding due to excessive anticoagulation and line disconnections, fluid and electrolyte imbalance, and filter and venous clotting. CRRT can complicate the medication regimens of patients for whom it is important to maintain drug plasma concentrations within a narrow therapeutic range. Since the physicochemical characteristics of a drug and procedure-specific factors can alter drug removal, a thorough assessment of all factors needs to be considered before dosage regimens are revised. In addition, an algorithm for drug dosing considerations based on drug and CRRT characteristics, as well as standard pharmacokinetic equations, is proposed. CONCLUSIONS: The use of CRRT has expanded to encompass the treatment of disease states other than just acute renal failure. Since there is great variability among treatment centers, it is premature to conclude that there is enhanced survival in CRRT-treated patients compared with those who received conventional hemodialysis. This primer may help clinicians understand the need to individualize these therapies and to prospectively optimize the pharmacotherapy of their patients receiving CRRT.     

Automatic continuous venovenous hemodiafiltration in cardiosurgical patients

Intermittent substitutive treatments in severely ill patients with acute renal failure are difficult or not suitable because of technical problems and/or hemodynamic instability. Continuous venovenous hemodiafiltration allows an adequate, slow removal of fluid, electrolytes, and waste products by combining diffusive and convective solute transport. Eight patients with acute renal failure, after cardiovascular surgery and cardiogenic shock, were treated by continuous venovenous hemodiafiltration. An automatic system (Equaline System, Amicon Division, USA) was employed. Venous accesses (femoral or subclavian) were used with double lumen catheters. A polysulfone filter (0.4 m2) was used in the study. Blood flow was 30 ml/min and dialysate flow rate 16.6 ml/min. Sterile pyrogen-free hemofiltration substitution fluid was used as dialysate. Mean duration of treatment was 10.3 +/- 3.2 days. After 72 hours blood urea nitrogen levels dropped from 136 +/- 46.13 to 53.5 +/- 12.3 mg/dl and creatinine levels dropped from 6.9 +/- 1.7 to 2.6 +/- 0.9 mg/dl. A controlled steady-state was then maintained. Mean urea clearance was 21 +/- 5.3 ml/min; mean ultrafiltration rate was 20.3 +/- 4.1 L/day. Continuous venovenous hemodiafiltration, with the Equaline System, is effective for the clearance of waste products and is able to maintain perfect fluid balance in catabolic patients with acute renal failure and multiple organ failure.     

Clinical evaluation of a continuous intra-arterial blood gas system in critically ill patients

OBJECTIVE: To evaluate the clinical performance of a new, continuous intra-arterial blood gas monitoring system (CIABG) in abnormal ranges of blood gases, and during episodes of low blood pressure, in critically ill patients. DESIGN: Prospective study. SETTINGS: Medical ICU, University Hospital. METHODS: The CIABG system, based on fluorescent dyes, consists of a fiber-optic sensor introduced through an arterial catheter. Twenty-one sensors were evaluated in 15 acutely ill patients. A high failure rate (6/21) was found, due to the brittleness of the fibers. The bias, between CIABG and standard method, and precision were determined for each fiber and for the overall values. Analysis focused on the data collected in patients with arterial oxygen tension (PaO2) values below 75 mmHg, pH lower than 7.35 and arterial carbon dioxide partial pressure (PaCO2) values exceeding 50 mmHg and during episodes of low blood pressure. The accuracy of the CIABG to follow sequential changes in blood gases was studied among the abnormal values. RESULTS: Measurements with CIABG among the abnormal values showed biases of +2mmHg, +0.1mmHg and +0.005 for PaO2, PaCO2 and pH, respectively, and precisions of 9.0mmHg, 3.5mmHg and 0.027, respectively. Bias and precision were not influenced by hemodynamic instability. A substantial difference in the performance of individual CIABG was observed for PaO2 analysis, with 30% of the fibers having a much poorer performance than the others. The sensors were kept in place for 5 +/- 2 days and the drift rate per day was 0.005 for pH, 0.6mmHg for PaCO2 and -1.2mmHg for PaO2. CONCLUSION: In situations of severe hypoxemia, hypercapnia and acidosis, the agreement between CIABG and arterial blood sampling (ABS) is better for PaCO2 and pH than for PaO2, and is not influenced by episodes of low blood pressure.     

Reversing oliguria in critically ill patients

Oliguria is a common occurrence in the ICU setting. In patients with preserved renal function, fluid challenges or low doses of diuretics are generally successful. In patients with oliguric renal failure, it is still essential to ensure adequate intravascular fluid volume, especially in critically ill patients. Loop diuretics remain the mainstay of treatment. When diuretic resistance is encountered, physicians should consider further optimization of hemodynamics, alternative loop diuretics, and combined drug therapy. In some cases, continuous renal replacement therapy can be very effective. Yet, while these interventions can help reduce the morbidity of severe volume overload, they have not been shown to improve mortality rates.     

Nutritional support of critically ill patients

Severe depletion of body protein stores can result from prolonged starvation or from hormonal and cytokine-mediated effects during critical illness. Recent advances in the understanding of cytokine actions have substantially refined the interpretation of the nutritional assessment of critically ill patients. In addition, the design of nutritional programs for hospitalized patients has changed considerably during the past decade. Although nutritional support of critically ill patients will not lead to positive nitrogen balance, nutrition can increase protein synthesis, enhance immune function, and beneficially modify the body's response to an illness.     

Human growth hormone kinetics in critically ill patients

Several studies have shown that exogenous human growth hormone (HGH) exerts an anabolic effect on protein metabolism in surgical patients with mild or moderate catabolism. However, contradictory results have been demonstrated in polytrauma patients where HGH did not improve protein metabolism. Aim of this study was to evaluate whether the pharmacokinetics of recombinant biosynthetic human GH (r-HGH) are altered in critically ill patients. After an overnight fast, r-HGH was infused at a rate of 460 micrograms/h/kg/bw during 120 min to five intensive care unit (ICU) patients. The patients were catabolic (nitrogen balance -11 +/- 0.5), showed normal liver function, and only one patient had a slightly impaired kidney function (creatinine > 1.5 mg/dl). Endogenous GH secretion was suppressed by continuous infusion of 50 micrograms/m2/h somatostatin. From plasma GH curves, elimination half life (t1/2kle), whole body clearance (Cltot) and steady state distribution space (DS) were calculated in an open two compartment model. Additionally, the effects of r-HGH infusion on plasma insulin, glucagon and amino acid concentrations were evaluated. T1/2kle was 19.6 +/- 2.3 min, Cltot 2.9 +/- 0.4 ml/kg/bw/min and DS 76.4 +/- 3.8 ml/kg/bw for 90 min. The plasma levels of total amino acids including the branched chain amino acids valine, leucine and isoleucine and of glutamine were significantly higher during r-HGH infusion than during the basal and somatostatin periods. In conclusion, the elimination of r-HGH in catabolic ICU patients is not different from that of healthy volunteers.     

Evaluation of a continuous cardiac output and mixed venous oxygen saturation catheter in critically ill surgical patients

OBJECTIVE: To evaluate the agreement of continuous cardiac output and mixed venous oxygen saturation measurements, obtained with a modified pulmonary artery catheter, with those values obtained by standard intermittent bolus thermodilution and cooximetry. DESIGN: Prospective, clinical investigation. SETTING: A surgical intensive care unit in a tertiary referral center. PATIENTS: Twenty-one adult critically ill surgical patients, requiring pulmonary artery catheter monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A modified pulmonary artery catheter capable of continuous monitoring of cardiac output and mixed venous oxygen saturation was used with either an 8.5-Fr or a 9-Fr introducer. At random intervals, the continuous cardiac output measurement was compared with the cardiac output obtained using standard intermittent bolus thermodilution. The system was calibrated every 24 hrs for mixed venous oxygen saturation monitoring. Each saturation obtained by the laboratory cooximeter was compared with that value recorded using the catheter. Data points for 202 pairs of cardiac output (21 patients, 31 catheters) and 65 pairs of mixed venous oxygen saturation (20 patients, 28 catheters) were obtained. The bias and precision of the cardiac output data were 0.49 and 1.01 L/min, respectively. The agreement between the continuous and bolus values decreased as the cardiac output increased. Heart rate did not affect the agreement between the continuous and bolus techniques. The bias and precision of the mixed venous oxygen saturation data were -0.57% and 3.76%, respectively. The hematocrit did not affect the bias or precision of the venous saturation data over the hematocrit range observed (23.2% to 44.6%). Fewer catheter malfunctions were observed when the catheter was used with a 9-Fr introducer than with an 8.5-Fr introducer. CONCLUSIONS: The test catheter adequately measures continuous cardiac output and mixed venous oxygen saturation in the clinical setting. Because intermittent bolus thermodilution is not a true "gold standard" for cardiac output determination, new techniques compared with bolus thermodilution may fail to achieve accuracy expectations. A 9-Fr introducer is recommended, as fiberoptic damage may have occurred when the 8.5-Fr introducer was used.     

Predictability of creatinine clearance estimates in critically ill patients

OBJECTIVES: a) To evaluate the predictive ability of different creatinine clearance methods as compared with the criterion standard, inulin clearance; and b) to determine which of the predictive methods yields the most accurate estimation of creatinine clearance. DESIGN: Prospective study. SETTING: Medical intensive care unit (ICU) of a university-affiliated tertiary care hospital. INTERVENTIONS: Glomerular filtration rate was measured by the criterion standard, inulin clearance. PATIENTS: Twenty mechanically ventilated adults. MEASUREMENTS: Renal function was assessed by the following procedures: inulin clearance using a standard protocol, 30-min creatinine clearance, 24-hr creatinine clearance, and creatinine clearance estimates by the Cockcroft-Gault equation. Ideal body weight, total body weight or lean body mass with actual serum creatinine or serum creatinine concentration corrected to 1 mg/dL (85 mumol/L) in cachectic patients were sequentially incorporated into the Cockcroft-Gault equation. RESULTS: The Cockcroft-Gault equation, using ideal body weight and the corrected serum creatinine concentration, was the best predictor of inulin clearance with the smallest bias (9.7 +/- 8.6, 95% confidence interval 5.7 to 13.8). The bias encountered with the 30-min creatinine clearance was not different from that value with the 24-hr creatinine clearance (21.6 +/- 33.0, 95% confidence interval 6.2 to 37.1 vs. 25.4 +/- 28.3, 95% confidence interval 11.8 to 42.9). Good correlations existed between inulin clearance and the Cockcroft-Gault equation, using ideal body weight and the corrected serum creatinine concentration (r2 = .81; p = .0001), as well as between inulin clearance and the Cockcroft-Gault equation, using the lower of ideal or total body weight and the higher of the actual serum creatinine concentration or corrected serum creatinine (r2 = .75; p = .0001). The 30-min creatinine clearance and the 24-hr creatinine clearance had poorer agreement with inulin clearance. The incorporation of a corrected serum creatinine value into the Cockcroft-Gault equation consistently led to better predictions and higher correlation coefficients. CONCLUSIONS: The utilization of the Cockcroft-Gault equation as used clinically (the lower of ideal or total body weight and the higher of actual serum creatinine or corrected serum creatinine concentration to 1 mg/dL [85 mumol/L]) results in more accurate predictions of glomerular filtration rate in the medical, critically ill patient than urine creatinine clearance measures. If creatinine clearance measures are used, the 30-min collection provided results not different from those results obtained with 24-hr urinary collections.     

Portable power supply for continuous mechanical ventilation during intrahospital transport of critically ill patients with ARDS

Patients with respiratory failure and poor pulmonary compliance requiring high levels of positive pressure ventilation are at high risk during intrahospital transportation. Most ICU ventilators currently do not have a built-in power supply. Manual bag-valve ventilation frequently is used but often without optimum mean airway pressures or minute ventilation guarantees. Transport ventilators also are limited in their ability to provide high positive end-expiratory pressure, variable inspiratory-expiratory ratios, or pressure-controlled ventilation. The 3M SARNS HELP (Hospital Emergency Limited Power) 115, a portable battery, provides continuous power to ICU ventilators and eliminates ventilator circuit interruption for the critical period of patient transportation.     

Bone hyperresorption is prevalent in chronically critically ill patients

STUDY OBJECTIVE: Chronically critically ill (CCI) patients are primarily elderly people who have survived a life-threatening episode of sepsis but remain profoundly debilitated and ventilator dependent. The objective of this study was to determine the prevalence of bone hyperresorption and parathyroid hormone (PTH)-vitamin D axis abnormalities in these patients. DESIGN: Prevalence survey. SETTING: Respiratory care step-down unit (RCU) at a tertiary care teaching hospital. PATIENTS: Forty-nine ventilator-dependent CCI patients transferred from ICUs within the same institution. INTERVENTION: None. MEASUREMENTS AND RESULTS: N-telopeptide (NTx) levels in 24-h urine collections and serum intact PTH, 25-vitamin D, and 1,25-vitamin D levels were measured within 48 h of RCU admission. Patients were hospitalized a median of 30 days before RCU admission. Four patients (9%) had normal NTx and PTH levels. Forty-five patients (92%) had elevated urine NTx levels consistent with bone hyperresorption. Nineteen patients (42% of total patients) had elevated PTH levels consistent with predominant vitamin D deficiency, 4 patients (9%) had suppressed PTH levels consistent with predominant hyperresorption from immobilization, and 22 patients (49%) had normal PTH levels consistent with an overlap of both vitamin D deficiency and immobilization. There were no differences in vitamin D metabolites among these groups. CONCLUSIONS: CCI patients have a high prevalence of bone hyperresorption in which PTH levels may clarify the cause. Further studies will determine the efficacy and cost-effectiveness of routine NTx and PTH screening in these patients and the role of vitamin D and antiresorptive therapies.