Alexandra Gendo

Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients.

ObjectivesTo investigate pharmacokinetics and metabolism of sodium citrate in critically ill patients. To determine the risk of citrate accumulation in the setting of liver dysfunction (cirrhosis, hepatorenal syndrome). DesignProspective cohort study. SettingIntensive Care Unit, Department of Medicine IV, University Hospital Vienna. PatientsConsecutive critically ill cirrhotic (n = 16) and noncirrhotic patients (n = 16). InterventionsInfusion of sodium citrate (0.5 mmol·kg−1·hr−1) and calcium chloride (0.17 mmol·kg−1·hr−1) for 2 hrs. Analysis of serial arterial blood samples. Measurements and Main ResultsTotal body clearance of citrate was normal in noncirrhotic critically ill patients but significantly reduced in cirrhotic patients (710 vs. 340 mL/min, p = .008). Citrate peak concentrations and concentration over time were increased by 65% and 114% in cirrhotic patients (p < .001), respectively; volumes of distribution were similar. Net metabolic changes were quantitatively similar, with pH and plasma bicarbonate concentrations increasing more slowly in cirrhotic patients. No citrate-related side effects were noted. Citrate clearance could not be predicted by standard liver function tests and was not appreciably influenced by renal function and Acute Physiology and Chronic Health Evaluation II scores. ConclusionsThis first systematic study on citrate pharmacokinetics and metabolism in critically ill patients confirms a major role of hepatic citrate metabolism by demonstrating reduced citrate clearance in cirrhotic patients. Pharmacokinetic data could provide a basis for the clinical use of citrate anticoagulation in critically ill patients. Provided dose adaptation and monitoring of ionized calcium, citrate anticoagulation seems feasible even in patients with decompensated cirrhosis. Metabolic consequences of citrate infusion were not different between groups in this study but may be more pronounced in prolonged infusion.

Improved outcome prediction in unconscious cardiac arrest survivors with sensory evoked potentials compared with clinical assessment

Objective: To compare the prognostic ability of sensory evoked potentials in cardiac arrest survivors with the outcome predicted by a panel of experienced emergency physicians based on detailed prehospital, clinical, and laboratory data. Design: Inception cohort study. Setting: Medical intensive care unit and department of emergency medicine at a university hospital. Patients: A total of 162 unconscious, mechanically ventilated patients who survived ≥24 hrs after resuscitation from cardiac arrest. Interventions: Recording of sensory evoked potentials and outcome prediction after review of detailed clinical and laboratory data by emergency physicians within 24 hrs after cardiac arrest. Measurements and Main Results: At 6 months, the outcome of 36 patients was classified as favorable and 126 patients were rated as poor. After review of prehospital data, emergency physicians predicted favorable vs. poor outcome with a sensitivity of 70% and a specificity of 65%. After additional assessment of data 1 hr after cardiac arrest, the sensitivity of emergency physician predictions increased to 80%, whereas the specificity decreased to 48%. Outcome prediction by emergency physicians was most accurate after obtaining detailed patient data 24 hrs after cardiac arrest (sensitivity, 81%; specificity, 58%). In 35 of 36 patients with favorable outcomes, the cortical evoked potential N70 peak was detected between 72 and 128 msec. Of 113 patients with an N70 peak latency > 130 msec or an absent N70 peak, all except one had a poor outcome. By using a cutoff of 130 msec, the N70 peak latency alone had a sensitivity of 94% and a specificity of 97%. The predictive accuracy of the N70 peak latency was significantly higher than the clinical assessment 24 hrs after cardiac arrest (91% vs. 76%, p = .0003). Conclusion: In unconscious cardiac arrest survivors, a recording of long‐latency sensory evoked potentials is more accurate in predicting individual outcome than an emergency physician review of clinical data.

Impaired subcortical and cortical sensory evoked potential pathways in septic patients.

ObjectiveSensory evoked potential (SEP) peak latencies were recorded in order to evaluate the incidence and severity of septic encephalopathy, testing the hypothesis that the occurrence of septic encephalopathy is more frequent than generally assumed. DesignProspective cohort study. SettingMedical intensive care unit of a university hospital. PatientsSixty-eight critically ill patients were studied within 48 hrs after the development of severe sepsis (n = 41) or septic shock (n = 27). InterventionsNone. Measurements and Main ResultsSeptic encephalopathy was defined as prolongation of SEP peak latencies beyond the upper limit of the reference range of subcortical (N13–N20 interpeak latency) and cortical SEP pathways (N20–N70 interpeak latency), as well as asymmetry of peak latencies marked by the presence of subclinical cerebral focal signs. Subcortical SEP pathways were impaired in 34% and cortical SEP pathways in 84% of all patients. The prolongation of the cortical SEP pathway correlated with the Acute Physiology and Chronic Health Evaluation III score (r = 0.23;p < .0001). SEP peak latencies did not differ in patients with severe sepsis compared with those with septic shock. Subclinical cerebral focal signs were present in 24% of the subcortical SEP pathways and in 6% of the cortical SEP pathways. ConclusionsSeptic encephalopathy occurs more frequently than generally assumed, and its severity is associated with the severity of illness. The impairment of subcortical and cortical SEP pathways was not different between patients with severe sepsis and those with septic shock.

Metabolic encephalopathy in critically ill patients suffering from septic or nonseptic multiple organ failure

Objective: Evaluation of changes in the peak latencies of sensory evoked potentials in different patient groups, to evaluate differences in metabolic encephalopathy of critically ill patients with multiple organ failure as a result of septic or nonseptic conditions. Design: Prospective cohort study. Setting: Intensive care units of the university hospital, Vienna. Patients: Patients (n = 103) treated on an intensive care unit because of multiple organ failure with additional metabolic encephalopathy. Multiple organ failure was induced by sepsis (group A; n = 56), surgery (group B; n = 29), or both (group C; n = 18). Interventions: None. Measurements and Main Results: Metabolic encephalopathy was determined by measuring median nerve‐stimulated short‐latency and long‐latency sensory evoked potentials. No differences in the peak latencies of the sensory evoked potentials were detected among the groups. Septic patients had a N70 peak latency of 131 ± 21 msecs, nonseptic postsurgical patients of 132 ± 17 msecs, and septic postsurgical patients of 134 ± 17 msecs. The cervicomedullary N13 to cortical N20 conduction times were 6.4 ± 1 msec, 6.4 ± 1.4 msecs, and 6.8 ± 1.2 msecs, respectively. All measured peak latencies were significantly prolonged compared with peak latencies of healthy controls. The severity of illness assessed by the Acute Physiology and Chronic Health Evaluation III score was not different between the three groups. An increase of the delay of N70 peak latencies was significantly correlated with the severity of illness (r2 = .15; p < .00005). Conclusion: There was no difference in sensory evoked potential measurements detectable among septic patients with multiple organ failure, nonseptic postsurgical patients with multiple organ failure, and septic postsurgical patients with multiple organ failure. The N70 peak latency was significantly correlated with the severity of illness but not with the presence or absence of sepsis. In postsurgical patients with multiple organ failure and superimposed sepsis, the N70 peak latencies were not further prolonged compared with postsurgical patients without sepsis.

A controlled study of sorbent suspension dialysis in chronic liver disease and hepatic encephalopathy.

To investigate the role of extracorporeal detoxification in cirrhotic patients with advanced hepatic encephalopathy not responding to medical treatment, 20 patients were randomized to receive six hours of additional sorbent dialysis or ongoing standardized medical treatment. Following treatment, the clinical stage of encephalopathy remained unchanged in both groups. Abnormal sensory evoked potentials improved following sorbent dialysis (N70 latency, 128 ms before versus 110 ms after treatment, P<0,05; cervico-cranial transmission, 7.7 ms versus 6.8 ms, P<0.01) indicating improvement in important aspects of cerebral function. In contrast, brain function remained unchanged following medical treatment (N70 latency, 114 ms versus 113 ms; cervico-cranial transmission, 7.7 ms versus 7.2 ms, P=NS, respectively). Serum benzodiazepine levels decreased significantly after sorbent dialysis but not after medical treatment. Biocompatibility of sorbent dialysis was limited and clinical complications occurred in a proportion of patients. In conclusion, a six-hour treatment with sorbent suspension dialysis did not ameliorate the clinical stage of HE but improved neurophysiologic function in cirrhotic patients who had not responded to conventional medical treatment.

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.

Electropyhsiological assessment of the afferent sensory pathway in cardiac arrest survivors

Background Hypoxic‐ischaemic brain damage in cardiac arrest survivors is global, but postmortem histology could identify parts of the brain that are selectively vulnerable to ischaemia, comprising the thalamus and cortex. We hypothesized that hypoxic‐ischaemic brain damage increases along the afferent sensory pathway with a stepwise decrease of detectable somatosensory evoked potential peaks.

Prognostic accuracy of sensory evoked potentials (SEP) and arterial ammonia in predicting development of cerebral edema and death by cerebral herniation in patients with fulminant hepatic failure (FHF)

Cerebral edema, leading to cerebral herniation, is still a major clinical complication and a common cause of death in patients with FHF. Recording of SEP, an objective parameter of cerebral function, has been proposed to predict the neurological course in patients with FHF. Recently, it has been demonstrated that high arterial ammonia is associated with later death by cerebral herniation. We compared the prognostic accuracy of SEP and arterial ammonia in predicting development of cerebral edema and death from cerebral herniation. We included 54 patients (31 females,aged 36:!:19 years) with FHF. The worst N70 peak latency of SEP and the highest arterial ammonia level within 72 hours after emerge of hepatic encephalopathy grade no was used for analysis. Critical cutoff points were defined as 1.) presence or absence of cortical N70 peaks and 2.) arterial ammonia levels below or above 145 ILmoIIL. 21 patients (39%) developed a loss of the N70 peak and 27 patients (50%) had arterial ammonia levels> 145 ILmoIIL. 26 patients (48%) developed cerebral edema and 16 of those (62%) died from cerebral herniation. Out of 21 patients without N70 peak, all but one developed cerebral edema, but only 13 patients died from cerebral herniation. In contrast, out of 27 patients with arterial ammonia < 145 ILmoIIL, 4 patients developed cerebral edema and only 2 patients died from cerebral herniation. Patients who died from cerebral herniation had higher arterial ammonia concentrations (259:!:167 vs 130:!:106 ILmoIIL; p=O.OOI). The prognostic values of SEP and arterial ammonia are shown in the table. In FHF, recording of SEP has a high predictive accuracy to detect patients at risk of developing cerebral edema but fails to predict later death from cerebral herniation. In contrast, assessment of arterial ammonia fails to identify patients at risk of developing cerebral edema but allows detection of patients without risk of cerebral herniation.

Influence of hydroxy ethyl starch infusion on serum bilirubin levels in cirrhotic patients treated with artificial liver support.

Serum bilirubin levels are commonly used to assess extracorporeal detoxification by liver support systems. We tested the hypothesis that intravenous colloids administered before liver support treatment could confound bilirubin values. Eight cirrhotic patients received an infusion of a 6% hydroxy ethyl starch solution (10 ml/kg, 30 minutes) before detoxification using a liver support system (FPSA). Bilirubin was measured before and 1 hour after infusion, and after FPSA treatment (7 hours). Infusion of hydroxy ethyl starch was associated with a drop in bilirubin values (mean, 18%, range, 1–44%, p=0.03 versus baseline values). Bilirubin levels were further reduced during FPSA treatment (mean, 27%, range, 22–34%; p=0.02 versus pre-treatment values). In conclusion, hydroxy ethyl starch solution may decrease bilirubin levels in hyperbilirubinemic cirrhotic patients receiving extracorporeal detoxification. The role of potentially confounding factors in liver support studies is discussed further.