Correlation of calculated indices of insulin resistance (QUICKI and HOMA) with the euglycaemic hyperinsulinaemic clamp technique for evaluating insulin resistance in critically ill patients.

BACKGROUND AND OBJECTIVE: Insulin resistance is frequently observed in critical illness. It can be quantified by the expensive and time-consuming euglycaemic hyperinsulinaemic clamp technique (M-value) and calculated indices of insulin resistance (Quantitative Insulin Sensitivity Check Index; QUICKI and Homeostasis Model Assessment; HOMA) with lower costs and efforts. We performed an observational study to assess the reliability of QUICKI and HOMA to evaluate insulin resistance in critically ill patients compared with the current gold standard method, the euglycaemic hyperinsulinaemic clamp technique. METHODS: Insulin resistance was measured in 30 critically ill medical patients by the euglycaemic hyperinsulinaemic clamp technique (M-value) as well as calculated using QUICKI and HOMA. Correlations between the M-values as well as QUICKI and HOMA were assessed by means of the Pearson's correlation coefficient. RESULTS: M-value, QUICKI and HOMA indicated insulin resistance in all 30 patients. However, both indices QUICKI and HOMA did not correlate with the M-values in our patients (r2 = 0.008 and 0.0005, respectively). A significant negative correlation was found between the M-value and the severity of illness assessed by the APACHE (Acute Physiology and Chronic Health Evaluation) III score (r2 = 0.16; P < 0.05). In contrast, neither HOMA nor QUICKI correlated with the APACHE III score (r2 = 0.034 and 0.033, respectively). CONCLUSIONS: Although QUICKI and HOMA indicated insulin resistance in the critically ill medical patients, both indices did not correlate with the M-value. Therefore, the euglycaemic hyperinsulinaemic clamp technique remains the gold standard for estimating insulin resistance in critically ill patients.

Energy and substrate metabolism in patients with chronic extensive graft-versus-host disease.

BACKGROUND: Allogeneic stem cell transplantation is frequently complicated by graft-versus-host disease (GVHD). Weight loss is one of the characteristic features of GVHD. The etiology of weight loss in GVHD is not completely understood. METHODS: We measured resting energy expenditure (REE) and substrate oxidation rates by indirect calorimetry in patients with stable chronic extensive GVHD under immunosuppressive therapy (n=13) and sex-, age-, height-, and weight-matched healthy controls (n=13) in order to evaluate metabolic changes in these patients. Measurements were done on day 518+/-261 after allogeneic stem cell transplantation in the postabsorptive state. Serum concentrations of glucagon, norepinephrine, tumor necrosis factor-alpha, interleukin-6, and free fatty acids were determined. RESULTS: Patients showed a maximum weight loss of 22% during their course of GVHD; nevertheless, they regained 15% of total body weight (TBW) during successful treatment of GVHD. Indirect calorimetry showed an increase in REE per kilogram of TBW (patients, 21.8+/-3.1 kcal/kg TBW/day; controls, 19.9+/-2 kcal/kg TBW/day; P<0.05). Respiratory quotient (patients, 0.79+/-0.04, controls, 0.86+/-0.04; P<0.005) and non-protein respiratory quotient (0.78+/-0.05 and 0.87+/-0.05, respectively; P<0.005) were decreased in patients. GVHD patients had elevated serum glucagon and norepinephrine concentrations, whereas tumor necrosis factor-alpha and interleukin-6 were in the normal range. CONCLUSIONS: Patients with chronic extensive GVHD show an increase in REE and alterations in fat and carbohydrate oxidation rates. These changes seem to be the result of increased action of glucagon and norepinephrine.

Short-term prognosis in critically ill patients with liver cirrhosis: an evaluation of a new scoring system.

OBJECTIVE: The mortality of patients with liver cirrhosis admitted to an intensive care unit (ICU) has been found to be high. This study was performed to assess the physiological and laboratory parameters which are able to identify on ICU admission the cirrhotic patients who are most likely to die. DESIGN: Prospective clinical trial. METHODS: Two groups of patients were analysed. Group A consisted of 196 consecutive cirrhotic patients admitted to our medical ICU for various reasons. For the detection of independent outcome predictors, we used a multiple logistic regression model. Based on these variables, the 'intensive care cirrhosis outcome (ICCO) score' was calculated. The ability to discriminate between survivors and non-survivors was determined by receiver operating characteristic curves, and the area under the curve was calculated. Group B consisted of 70 consecutive cirrhotic patients for prospective validation of the ICCO score. RESULTS: Applying multiple logistic regression analysis, bilirubin, cholesterol, creatinine clearance and lactate were found to be independently associated with the hospital mortality. The ICCO score was 0.3707 + (0.0773 x bilirubin (mg/dl)) - (0.00849 x cholesterol (mg/dl)) -(0.0155 x creatinine clearance (ml/min)) + (0.1351 x lactate (mmol/l)), giving an area under a receiver operating characteristic curve of 0.9. Increasing score values were associated with an increase in mortality. All patients with an ICCO score > +2.6 died. CONCLUSIONS: Application of the ICCO score is rapid and available at the patient's bedside, and its application is simple and reproducible. In cirrhotic patients, the ICCO score has a high ability to discriminate between survivors and non-survivors. The ICCO score may facilitate estimation on ICU admission of the prognosis of critically ill cirrhotic patients.

Resting energy expenditure in short-term starvation is increased as a result of an increase in serum norepinephrine.

BACKGROUND: The effects of food restriction on energy metabolism have been under investigation for more than a century. Data obtained are conflicting and research has failed to provide conclusive results. OBJECTIVE: The objective of this study was to test the hypothesis that in lean subjects under normal living conditions, short-term starvation leads to an increase in serum concentrations of catecholamines and thus to an increase in resting energy expenditure. DESIGN: Resting energy expenditure, measured by indirect calorimetry, and hormone and substrate concentrations were measured in 11 healthy, lean subjects on days 1, 2, 3, and 4 of an 84-h starvation period. RESULTS: Resting energy expenditure increased significantly from 3.97 +/- 0.9 kJ/min on day 1 to 4.53 +/- 0.9 kJ/min on day 3 (P < 0.05). The increase in resting energy expenditure was associated with an increase in the norepinephrine concentration from 1716. +/- 574 pmol/L on day 1 to 3728 +/- 1636 pmol/L on day 4 (P < 0.05). Serum glucose decreased from 4.9 +/- 0.5 to 3.5 +/- 0.5 mmol/L (P < 0.05), whereas insulin did not change significantly. CONCLUSIONS: Resting energy expenditure increases in early starvation, accompanied by an increase in plasma norepinephrine. This increase in norepinephrine seems to be due to a decline in serum glucose and may be the initial signal for metabolic changes in early starvation.

Mild resuscitative hypothermia to improve neurological outcome after cardiac arrest. A clinical feasibility trial. Hypothermia After Cardiac Arrest (HACA) Study Group.

BACKGROUND AND PURPOSE: Recent animal studies showed that mild resuscitative hypothermia improves neurological outcome when applied after cardiac arrest. In a 3-year randomized, prospective, multicenter clinical trial, we hypothesized that mild resuscitative cerebral hypothermia (32 degrees C to 34 degrees C core temperature) would improve neurological outcome after cardiac arrest. METHODS: We lowered patients' temperature after admission to the emergency department and continued cooling for at least 24 hours after arrest in conjunction with advanced cardiac life support. The cooling technique chosen was external head and total body cooling with a cooling device in conjunction with a blanket and a mattress. Infrared tympanic thermometry was monitored before a central pulmonary artery thermistor probe was inserted. RESULTS: In 27 patients (age 58 [interquartile range [IQR] 52 to 64] years; 7 women; estimated "no-flow" duration 6 [IQR 1 to 11] minutes and "low-flow" duration 15 [IQR 9 to 23] minutes; admitted to the emergency department 36 [IQR 24 to 43] minutes after return of spontaneous circulation), we could initiate cooling within 62 (IQR 41 to 75) minutes and achieve a pulmonary artery temperature of 33+/-1 degrees C 287 (IQR 42 to 401) minutes after cardiac arrest. During 24 hours of mild resuscitative hypothermia, no major complications occurred. Passive rewarming >35 degrees C was accomplished within 7 hours. CONCLUSIONS: Mild resuscitative hypothermia in patients is feasible and safe. A clinical multicenter trial might prove that mild hypothermia is a useful method of cerebral resuscitation after global ischemic states.

Bladder volume determination: portable 3-D versus stationary 2-D ultrasound device.

OBJECTIVE: To investigate how accurately a portable three-dimensional (3-D) scanner and a multipurpose two-dimensional (2-D) real-time scanner determined bladder volumes. STUDY DESIGN: Prospective, controlled clinical trial, single-blind, crossover design. SETTING AND PARTICIPANTS: Twenty-three inpatients with permanent bladder catheters participated voluntarily in this study. METHODS: The bladders of 20 patients were filled through an indwelling catheter with 60, 110, 160, 210, and 260 mL sterile normal saline. Volumes were measured twice with each device. Measurements were compared with the actual bladder volumes. RESULTS: The 2-D device showed better reproducibility, particularly at lower bladder volumes. The 3-D scanner showed a significant difference between the two measurements at 160 mL (p<.05) and had poor reproducibility at 110, 210, and 260 mL. Both devices overestimated actual bladder volume at fillings of <160 mL and underestimated it at fillings of > or =160 mL. The range between the 25th and 75th percentiles was always larger for the 3-D scanner, except for the 210 mL reading. CONCLUSION: Both devices showed sufficient accuracy for clinical practice. Ultrasound measurements of >110 mL should be followed by catheterization to detect potentially harmful bladder volumes.

Alterations in angiotensin II release and vascular reactivity in hypertensive men: a pilot study.

Cold- and insulin-mediated release of angiotensin II (AII) and endothelin-1 (ET-1), as well as vascular reactivity to exogenous ET-1 and to insulin, were compared in hypertensive and normotensive subjects. Peripheral vascular release of AII and of ET-1 was investigated in 10 hypertensive (H; 29.2+/-5.8 years) and 12 normotensive (N; 29.1+/-4.6 years) men in two separate trials. Net transfemoral balance of AII and of ET-1 was calculated from the respective Arterio-Venous (A-V) differences in plasma concentrations (PC) of the peptides and the regional plasma flow (indocyanine-green dye method), both at baseline conditions and after a cold stimulus (immersion of one hand into ice water) in 7H and 6N, or during short-time hyperinsulinemia (hyperinsulinemic euglycemic clamp: biosynthetic human insulin, 1 mU/kg/min) in 7H and 7N. Moreover, hemodynamic changes to sequential exogenous ET-1 infusion (1, 2.5, 5, 10, 20, 40 ng/min) or during hyperinsulinemic clamp were studied in 7H and 6N and 7H and 7N, respectively. Baseline net-transfemoral balance of ET-1 and of AII were similar in the two subject groups. The cold stimulus provoked a similar increase in transfemoral ET-1 release in H and N (H: 257.0+/-31.7 to 526.2+/-393.7 pg/min; N: 280.2+/-112.7 to 524.0+/-393.7 pg/min, mean +/- SD, P<.05). In contrast, the cold-induced increase in transfemoral AII release was somewhat more pronounced in H than in N (H: 162.2+/-304.6 to 1081.7+/-1037.7 pg/ min, P<.05; N: 83.9+/-166.3 to 317.6+/-187.8 pg/ min, P<.02; maximum value H v. N P<.05). During the hyperinsulinemic clamp the PC of insulin increased from 5.8+/-2.8 to 69.1+/-15.5 microU/ mL in H and from 4.6+/-1.7 to 67.5+/-9,5 microU/mL in N; P<.0005. Hyperinsulinemia induced a similar elevation of norepinephrine PC in H and N, but an increase in transfemoral ET-1 release in N only (219.7+/-161.2 to 512.2+/-279.0 pg/min, P<.02). In contrast, hyperinsulinemia increased transfemoral AII formation in H (730.4+/-554.3 to 1088.6+/-597.9 pg/min, P<.05), but not in N. Insulin-mediated vasodilation was observed only in N, whereas ET-1-induced vasoconstriction was blunted in H. We conclude that the cold-induced increase in peripheral vascular release of AII is more pronounced in H than in N, whereas insulin provokes an increase in AII formation in hypertensives only. Moreover, insulin-mediated vasodilation and ET-1-dependent vasoconstriction are blunted in hypertensive subjects.

Heavy chronic alcohol abuse has no additional adverse effect on the function of extrahepatic organs and ICU mortality in patients with liver cirrhosis.

BACKGROUND AND AIMS: We questioned whether heavy chronic alcohol abuse influences extrahepatic organ failure and ICU mortality in cirrhotic patients admitted to a medical intensive care unit. PATIENTS AND METHODS: Medical records of 208 consecutive cirrhotic critically ill patients were reviewed. Patients were classified into two groups. Group A comprised 144 patients with liver cirrhosis due to heavy chronic alcohol abuse and group B, 64 patients with liver cirrhosis due to non-alcoholic causes. The presence of extrahepatic organ failures in patients of both groups was assessed with parameters determined on the day of admission to the ICU. Furthermore, ICU mortality was determined. RESULTS: The occurrence of extrahepatic organ failure was similar in group A and group B (83% vs. 80%; p = NS). The rate of extrahepatic organ failure was 1.7 +/- 1.2 organs in group A, compared to 1.4 +/- 1 organs in group B (p = NS). ICU mortality was 53% in group A and 44% in group B (p = NS). An increase in the number of extrahepatic organ failures was associated with a concomitant increase in ICU mortality in both groups of patients. CONCLUSION: The occurrence of extrahepatic organ failure and ICU mortality was not different between patients with liver cirrhosis secondary to heavy chronic alcohol abuse and patients with liver cirrhosis due to nonalcoholic causes. Cirrhotic patients should be admitted to a medical intensive care unit for extended intensive care treatment prior to the occurrence of extrahepatic multiple organ failure, independent of the underlying aetiology.

Epinephrine transiently increases amino acid disappearance to lower amino acid levels in humans.

BACKGROUND: Infusion of epinephrine decreases plasma amino acid concentrations. However, the mechanism by which this decrement occurs is not well characterized. METHODS: Epinephrine was infused (40 ng/kg/min) for 2 hours into eight normal healthy adults. The essential amino acid tracers L-[1-(13)C]leucine and L-[phenyl-2H5]phenylalanine were infused before and during the epinephrine infusion and blood samples obtained to determine amino acid rates of appearance and disappearance from the time course of change in amino acid concentration and tracer enrichments. RESULTS: Epinephrine infusion decreased plasma leucine and phenylalanine concentrations over a period of 30 to 90 minutes after the start of the epinephrine infusion. Epinephrine infusion induced an immediate decrement in tracer enrichments. These changes defined sharp increases in both rate of appearance and rate of disappearance. By 30 minutes of epinephrine infusion, the rate of amino acid appearance from proteolysis had returned to baseline, but the rate of amino acid disappearance remained elevated for 90 minutes before returning to baseline. It was the protracted increase in amino acid disappearance that was responsible for the lowering of plasma amino acid concentrations. After this acute response, rates of amino acid appearance and disappearance returned to normal whereas plasma amino acid levels remained suppressed. CONCLUSIONS: Epinephrine transiently affects both rates of amino acid appearance and disappearance, with the net effect being increased in amino acid disappearance. However, epinephrine lowers amino acid concentrations beyond the period that it affects kinetics. These results suggest that the effect of epinephrine on amino acid metabolism is not detrimental and that epinephrine allows amino acid metabolism to proceed normally but at lower concentrations of amino acids.

Inhalation of nitric oxide as a life-saving therapy in a patient after pulmonary embolectomy.

We describe a 54-yr-old man with cardiogenic shock caused by acute right heart failure after pulmonary embolectomy. Inhalation of nitric oxide led to immediate improvement in respiratory and haemodynamic variables. Inhaled nitric oxide can be used to reduce acute right heart failure until conventional therapy can provide successful haemodynamic stability.

Inhaled nitric oxide in a patient with severe pulmonary embolism.

We describe a 66-year-old woman with right-sided heart failure and cardiogenic shock resulting from severe pulmonary embolism. Her hemodynamic status improved dramatically with the use of inhaled nitric oxide. A proposed mechanism of action and a review of the literature are presented.

Epinephrine produces a prolonged elevation in metabolic rate in humans.

BACKGROUND: Epinephrine increases the metabolic rate and contributes to the hypermetabolic state in severe illness. OBJECTIVE: We sought to determine the effect of prolonged elevation of epinephrine on resting energy expenditure (REE). DESIGN: Thirteen healthy men were placed on a well-defined diet for 5 d. Beginning on the morning of the second diet day, the subjects were infused for 24 h with saline, then for 23 h with epinephrine (0.18 nmol x kg(-1) x min(-1)) to increase plasma epinephrine concentrations into the high physiologic range (4720 +/- 340 pmol/L). REE and the respiratory quotient (RQ) were measured by indirect calorimetry in the postabsorptive state at the same time every morning. RESULTS: Infusion of epinephrine significantly increased heart rate and systolic blood pressure, but the response was transient (values after 23 h of epinephrine infusion were not significantly different from those on the day saline was infused). Infusion of epinephrine significantly increased REE by 12% and increased the RQ. These changes were apparent at the end of the 23-h infusion (REE: 97.5 +/- 2.3 kJ x kg(-1) x d(-1) with saline infusion and 108.9 +/- 2.3 kJ x kg(-1) x d(-1) with epinephrine infusion; RQ: 0.832 +/- 0.012 with saline infusion and 0.879 +/- 0.013 with epinephrine infusion). REE returned to baseline by 24 h after the epinephrine infusion ended, but the postabsorptive RQ remained modestly elevated. Infusion of epinephrine also produced a transient increase in urine flow and in urinary nitrogen excretion. This diuresis was compensated for by a drop in urine volume and nitrogen excretion after the epinephrine infusion was stopped. CONCLUSIONS: Epinephrine produced a prolonged increase in REE in healthy subjects. The fuel for this increase in REE, determined by the RQ, was from increased carbohydrate oxidation, not from that of fat or protein.

[Prognostic factors in acute liver failure]. / Prognostische Faktoren bei akutem Leberversagen.

Acute liver failure is defined as acute severe, potentially reversible hepatic failure complicated by cerebral dysfunction. The high mortality rate of between 50% and 90% justifies early transfer to a specialised centre with the possibility of orthotopic liver transplantation to ensure adequate intensive care monitoring and treatment, 57 patients with acute liver failure (34 female, 23 male, aged 6 to 87 years, median 33 years) treated at our intensive care unit during the past 10 years were analysed retrospectively. Various factors and laboratory data were analysed in respect to their prognostic value. Depending on the aetiology, the survival rate in acute liver failure under conservative treatment ranges from 79% (amanita intoxication) to 10% (cryptogenic genesis). The most important predictive parameter is the extent of cerebral dysfunction. The extent of cerebral dysfunction is a determining factor of the survival rate under conservative treatment; it ranges from 94% (patients with hepatic encephalopathy grade I) to 11% (patients with hepatic encephalopathy grade IV). The occurrence of complications such as infections, cerebral oedema, respiratory failure or renal failure is also associated with an unfavourable outcome. Additionally, various laboratory parameters have a predictive ability. The mortality rate of our patients with acute liver failure has decreased from 56% to 32% since early intensive care monitoring and treatment and the possibility of acute orthotopic liver transplantation were established.

Single-dose pharmacokinetics of meropenem during continuous venovenous hemofiltration.

The pharmacokinetic properties of meropenem were investigated in nine critically ill patients treated by continuous venovenous hemofiltration (CVVH). All patients received one dose of 1 g of meropenem intravenously. High-flux polysulfone membranes were used as dialyzers. Meropenem levels were measured in plasma and ultrafiltrate by high-performance liquid chromatography. The total body clearance and elimination half-life were 143.7 +/- 18.6 ml/min and 2.46 +/- 0.41 h, respectively. The post- to prehemofiltration ratio of meropenem was 0.24 +/- 0.06. Peak plasma drug concentrations measured 60 min postinfusion were 28.1 +/- 2.7 microgram/ml, and trough levels after 6 h of CVVH were 6.6 +/- 1.5 microgram/ml. The calculated total daily meropenem requirement in these patients with acute renal failure and undergoing CVVH was 2,482 +/- 321 mg. Based on these data, we conclude that patients with severe infections who are undergoing CVVH can be treated effectively with 1 g of meropenem every 8 h.

Use of intravenous lipids in critically ill patients with sepsis without and with hepatic failure.

BACKGROUND: Fat is the preferred energy fuel both in patients with sepsis and with hepatic failure. Thus lipid emulsions should serve as an ideal nutritional substrate in parenteral nutrition. However, previous studies have generated conflicting results on the utilization of artificial lipids in these disease states, and systematic studies in critically ill patients with combined organ dysfunctions and additional complications are lacking. We compared the elimination, hydrolysis, and oxidation of a 20% lipid emulsion in critically ill patients on respiratory support with sepsis and with sepsis plus hepatic failure and in healthy control subjects. SETTING: Medical critical care unit of a university hospital. SUBJECTS AND METHODS: Eight critically ill patients with sepsis, 8 patients with sepsis and decompensated chronic hepatic failure, and 10 healthy volunteers were investigated. Elimination and hydrolysis was evaluated during constant i.v. infusion of 4.5 mg.kg body wt-1.min-1 of triglycerides during 120 minutes. Concentrations of plasma triglycerides, free fatty acids, and glycerol were measured, and elimination parameters were analyzed from plasma curves of triglycerides by using a two-compartment model. Resting energy expenditure and substrate oxidation were measured by indirect calorimetry. RESULTS: In patients with sepsis without and with hepatic failure the rise in plasma triglycerides was blunted and the clearance of triglycerides was enhanced by 20% and 40% (p < .05), respectively, compared with healthy controls. Basal free fatty acid concentrations were elevated, and the rise of free fatty acids and glycerol was comparable to healthy subjects. Energy expenditure was increased and lipid oxidation (as fraction of total energy expenditure) was slightly elevated in both patient groups; the rise in lipid oxidation during lipid infusion was comparable to controls. No side effects or impairment of gas exchange was seen. CONCLUSIONS: In a clinically relevant dosage range, the utilization of an i.v. lipid emulsion, the elimination and hydrolysis of triglycerides, and the lipid oxidation is not impaired in ventilated critically ill patients with sepsis or sepsis and chronic hepatic failure. Lipid emulsions thus are efficiently metabolized in critically ill patients with combined organ dysfunctions and associated sepsis.

Epinephrine does not impair utilization of exogenous amino acids in humans.

The effect of epinephrine on leucine and phenylalanine kinetics was measured by using the stable isotope amino acid tracers L-[1-(13)C]leucine and L-[phenyl-2H5]-phenylalanine in the postabsorptive state and during the intravenous administration of a standard amino acid solution with respect to the amino acid load. Infusion of epinephrine (plasma concentration: approximately 3600 pmol/L) decreased leucine and phenylalanine and increased ketoisocaproate plasma concentrations and increased the metabolic clearance rate of leucine and phenylalanine. Epinephrine neither influenced leucine or phenylalanine flux nor leucine oxidation or leucine net balance. Hyperaminoacidemia from amino acid infusion reduced endogenous leucine release and stimulated leucine oxidation and nonoxidative disposal of leucine, resulting in a dose-dependent increase in leucine net balance. Epinephrine did not influence any changes in amino acid kinetics during parenteral amino acid administration. Therefore, we conclude that epinephrine had no catabolic effects on amino acid metabolism and no negative effect on the utilization of a parenterally offered amino acid solution in healthy humans.

Detection of subclinical brain dysfunction by sensory evoked potentials in patients with severe diabetic ketoacidosis.

OBJECTIVE: Subclinical brain dysfunction is a potentially deleterious complication of diabetic ketoacidosis but is rarely recognized. Thus, we investigated the diagnostic value of sensory evoked potentials for detecting subclinical brain dysfunction in patients with diabetic ketoacidosis. DESIGN: Prospective trial. SETTING: Intensive care unit in a university hospital. PATIENTS: 5 neurologically asymptomatic patients (Glasgow Coma Scale score 15, slight drowsiness; aged 20 to 66 years) with an established diagnosis of severe diabetic ketoacidosis were studied. MEASUREMENTS AND RESULTS: Short- and long-latency sensory evoked potentials were recorded within 2 h of initiation of therapy for ketoacidosis and 7 days after normalization of ketoacidosis, respectively. Two hours after starting therapy, sensory evoked potential peak latencies were prolonged in all five patients compared to age-matched healthy subjects [cervical N 13 to cortical N 20 interpeak latency of short-latency evoked potentials (mean) 5.8 vs 5.3 ms, p < 0.05; N 35 peak latency 40 vs 34 ms, p < 0.05; N 70 peak latency of long-latency evoked potentials 102 vs 76 ms, p < 0.01]. In all five patients, cervical N 13 to cortical N 20 interpeak latency and N 35 and N 70 peak latency reverted to normal 7 days after recovery from diabetic ketoacidosis. CONCLUSIONS: Our study indicates that the recording of sensory evoked potentials is a sensitive method of detecting subclinical brain dysfunction in patients with severe diabetic ketoacidosis. Since sensory evoked potentials were significantly prolonged in all five patients, this strongly suggests that subclinical brain dysfunction occurs more frequently than is generally recognized.

Impairment of citrate metabolism in acute hepatic failure.

AIMS: To compare the utilization of citrate employed as anticoagulant in patients with acute hepatic failure and subjects with normal liver function. PATIENTS AND METHODS: Three patients in acute hepatic failure and normal renal function were studied during therapeutic plasma exchange with citrate containing fresh frozen plasma. Six patients receiving immunapheresis or LDL-apheresis anticoagulated with citrate served as controls. Determinations of serum citrate concentrations, of ionized calcium and blood pH were performed before, during, and after the extracorporeal treatment. Total body clearance and elimination half life were calculated in a two compartment model. RESULTS: Preinfusion citrate levels were higher in the patients with acute hepatic failure than in the controls (n.s.). The citrate level rose to 1.73 +/- 0.2 mmol/l in the liver patients versus 0.99 +/- 0.1 mmol/l in the healthy subjects (p < 0.03). Total body clearance was markedly reduced in patients with acute hepatic failure (3.31 +/- 0.03 ml/kg/min) as compared with the controls (6.34 +/- 0.16 ml/kg/min) (p < 0.02), the elimination half life (t/2 k1e) was prolonged (49.7 +/- 5.4 vs. 32.9 +/- 1.02 min, p < 0.05). In the controls blood pH rose from 7.4 +/- 0.01 to 7.45 +/- 0.01 (p < 0.05) after citrate infusion, whereas in the liver patients no rise in pH was observed, again reflecting the impairment of citrate metabolism. Ionized calcium was lower in the patients with acute hepatic failure at the beginning (1.01 +/- 0.05 vs. 1.21 +/- 0.04 mmol/l, p < 0.05) and the end (0.68 +/- 0.02 vs. 0.93 +/- 0.04 mmol/l, p < 0.05) of the citrate infusion. CONCLUSIONS: Citrate metabolism is severely impaired and the plasmatic calcium stores are reduced in acute hepatic failure and, thus, the risk of adverse effects is high. Therapeutic infusions of citrate should be restricted in patients with acute hepatic failure and, if necessary, therapy should be closely monitored by repeated measurements of ionized calcium to avoid the development of potentially hazardous hypocalcemia.